The DOI matches its Crossref record; 275 of the 278 references it cites were found in a registry or an index; 14 of the 250 sources its claims cite were checked for support.
AMPK, Mitochondrial Function, and Cardiovascular Disease
Open accessAbstract
Adenosine monophosphate-activated protein kinase (AMPK) is in charge of numerous catabolic and anabolic signaling pathways to sustain appropriate intracellular adenosine triphosphate levels in response to energetic and/or cellular stress. In addition to its conventional roles as an intracellular energy switch or fuel gauge, emerging research has shown that AMPK is also a redox sensor and modulator, playing pivotal roles in maintaining cardiovascular processes and inhibiting disease progression. Pharmacological reagents, including statins, metformin, berberine, polyphenol, and resveratrol, all of which are widely used therapeutics for cardiovascular disorders, appear to deliver their protective/therapeutic effects partially via AMPK signaling modulation. The functions of AMPK during health and disease are far from clear. Accumulating studies have demonstrated crosstalk between AMPK and mitochondria, such as AMPK regulation of mitochondrial homeostasis and mitochondrial dysfunction causing abnormal AMPK activity. In this review, we begin with the description of AMPK structure and regulation, and then focus on the recent advances toward understanding how mitochondrial dysfunction controls AMPK and how AMPK, as a central mediator of the cellular response to energetic stress, maintains mitochondrial homeostasis. Finally, we systemically review how dysfunctional AMPK contributes to the initiation and progression of cardiovascular diseases via the impact on mitochondrial function.
Overview
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Written from the paper’s full text.
TL;DR
This review argues that AMPK is both a redox sensor/modulator and a central regulator of mitochondrial homeostasis, with bidirectional crosstalk: mitochondrial dysfunction can alter AMPK activity, while AMPK controls mitochondrial biogenesis, dynamics, mitophagy, and Ca²⁺ handling. Dysregulated AMPK–mitochondria signaling contributes to cardiovascular disease, and drugs such as metformin, berberine, statins, polyphenols, and resveratrol may act partly through AMPK.
Key findings
- AMPK is a heterotrimeric complex of α, β, and γ subunits; all isoform combinations produce 12 different AMPK complexes. It is activated by AMP/ADP and inhibited by ATP, with LKB1 and CAMKK2 as major upstream kinases; Thr172 phosphorylation increases AMPK activity about 100-fold, while allosteric regulation changes activity up to tenfold in mammalian cells and about twofold in recombinant bacterially produced AMPK.
- AMPK functions as a redox sensor and antioxidant modulator: ROS/RNS can activate AMPK via energy stress and/or LKB1–CaMKK signaling, while activated AMPK suppresses mitochondrial and NOX-derived ROS and upregulates antioxidant genes including CAT, SOD1, SOD2, and UCP2, often through PGC1α.
- AMPK regulates mitochondrial homeostasis by promoting mitochondrial biogenesis via PGC1α, controlling mitochondrial dynamics through MFF phosphorylation at Ser155/Ser173 and DRP1, regulating mitophagy through ULK1 and PINK1–PARKIN signaling, and modulating mitochondrial Ca²⁺ influx through MCU.
- In cardiovascular disease, AMPK is generally protective across atherosclerosis, ischemia, ischemia/reperfusion injury, vascular calcification, neointimal hyperplasia, cardiac hypertrophy, diabetes, inflammation, and obesity; the review notes that reperfusion failure occurs in approximately 30% of patients with acute myocardial infarction and that ischemic heart disease accounted for 15.96% of total global deaths in 2017.
Methods
- Not stated in the paper; the text is a narrative review that synthesizes cited literature rather than presenting original experimental data.
- The review covers AMPK structure and regulation, redox regulation of AMPK, mitochondrial control of AMPK, AMPK regulation of mitochondrial homeostasis, and AMPK–mitochondria signaling in cardiovascular and cardio-metabolic diseases.
- Main analysis is qualitative synthesis of mechanistic studies across cell, animal, and some human contexts; no systematic search strategy, inclusion criteria, or meta-analysis is described.
Limitations
- Stated: the authors note that the functions of AMPK during health and disease are “far from clear” and that the interplay within the AMPK–mitochondrial axis during cardiovascular disease initiation and progression is poorly investigated.
- Stated: limited evidence has focused on mitochondrial dynamics, mitochondrial biogenesis, and mitophagy, and the structural and functional changes to mitochondria under disease conditions remain “far beyond our current knowledge.”
- Evident from the text: as a narrative review, it does not provide primary data, systematic evidence grading, or quantitative synthesis; many mechanistic conclusions are drawn from preclinical cell and animal models, with clinical evidence cited more selectively.
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Claims the paper makes
174 Not checked yet · 9 Own interpretation · 5 No basis given · 3 Supported · 2 Partly supported · 1 Supported so far · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Recent lines of evidence have demonstrated AMPK responsiveness to imbalanced redox status, thus bringing new insights into the networks of redox-stimulated signals upstream of AMPK (Table 1) [42,43,44,45,46,47,48,49,50,51].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [42] Liangpunsakul, 2008, Effect of ethanol on hydrogen peroxide-induced AMPK phosphorylation, Am. J. Physiol. Gastrointest. Liver Physiol. source
- Supportedcites [43] Han, Y., Wang, Q., Song, P., Zhu, Y., and Zou, M.H. (2010). Redox regulation of the AMP-activated protein kinase. PLoS ONE, 5. source
The Introduction reports that oxidant generation can lead to AMPK activation and states that berberine-induced activation is mediated by mitochondria-derived superoxide and peroxynitrite in endothelial cells. The Discussion likewise describes a role for these oxidants in AMPK activation, supporting the attributed claim that AMPK responds to redox changes. (LLM, conf=0.91)
- Supportedcites [44] Hinchy, 2018, Mitochondria-derived ROS activate AMP-activated protein kinase (AMPK) indirectly, J. Biol. Chem. source
The Abstract states that AMPK activity responds to redox changes, while specifying that the response is indirect rather than a direct action on AMPK. The Results/Conclusions likewise report altered AMPK activity after hydrogen peroxide exposure. This supports the citing sentence’s broad claim of responsiveness to redox status. (LLM, conf=0.90)
- Not checked yetcites [45] Choi, 2001, The regulation of AMP-activated protein kinase by H(2)O(2), Biochem. Biophys. Res. Commun. source
- Supportedcites [46] Hawley, 2010, Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation, Cell Metab. source
The Results report that hydrogen peroxide, a reactive oxygen species, activated AMPK in WT cells. The Discussion also states that oxidative stress activates AMPK, while suggesting the effect may be indirect, through respiratory-chain inhibition and altered cellular energy status. (LLM, conf=0.93)
- Not checked yetcites [47] McCullough, 2005, Pharmacological inhibition of AMP-activated protein kinase provides neuroprotection in stroke, J. Biol. Chem. source
- Supportedcites [48] Zmijewski, 2010, Exposure to hydrogen peroxide induces oxidation and activation of AMP-activated protein kinase, J. Biol. Chem. source
The paper’s opening summary reports that increased reactive oxygen species can stimulate AMPK activity and that H₂O₂ exposure increases its kinase activity through oxidative modification. This supports the claim that AMPK responds to imbalanced redox status. (LLM, conf=0.93)
- Supportedcites [49] Xie, 2006, Activation of protein kinase C zeta by peroxynitrite regulates LKB1-dependent AMP-activated protein kinase in cultured endothelial cells, J. Biol. Chem. source
The “LKB1-dependent AMPK activation” section reports that peroxynitrite, an oxidant, activated AMPK in several cell types and that inhibiting PKCζ attenuated this response. This supports the broad claim that AMPK responds to redox-related stress. (LLM, conf=0.91)
- Supportedcites [50] Wu, 2015, Activation of AMPKalpha2 in adipocytes is essential for nicotine-induced insulin resistance in vivo, Nat. Med. source
The Introduction calls AMPK a cellular “redox sensor,” and the Results section describes it as a key energy and redox sensor. These passages support the claim that AMPK responds to imbalanced redox status. (LLM, conf=0.92)
- Not checked yetcites [51] Rabinovitch, 2017, AMPK maintains cellular metabolic homeostasis through regulation of mitochondrial reactive oxygen species, Cell Rep. source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Nitrite is a dietary constituent that protects the heart against I/R injury in many animal models during both ischemia and preconditioning stage [186,187,188,189,190,191,192].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Partly supportedcites [186] Duranski, 2005, Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver, J. Clin. Investig. sourceExperimental — accuracy not yet measured
The section “Intraventricular nitrite limits myocardial I/R injury” reports that nitrite given to mice five minutes before reperfusion reduced myocardial infarct size. This supports protection during ischemia in a mouse model, but the paper does not establish protection during preconditioning or across many animal models. Its discussion of nitrite in cured meat does not establish the claimed dietary role in cardioprotection. (LLM, conf=0.88)
- Not checked yetcites [187] Tripatara, 2007, Nitrite-derived nitric oxide protects the rat kidney against ischemia/reperfusion injury in vivo: Role for xanthine oxidoreductase, J. Am. Soc. Nephrol. source
- Partly supportedcites [188] Jung, 2006, Early intravenous infusion of sodium nitrite protects brain against in vivo ischemia-reperfusion injury, Stroke sourceExperimental — accuracy not yet measured
The Discussion (page not provided) reports that nitrite protected against myocardial ischemia-reperfusion injury, citing prior work. It does not establish that nitrite is a dietary constituent or that it protects the heart in many animal models during both ischemia and preconditioning; this paper's own experiments concern the brain. (LLM, conf=0.88)
- Not checked yetcites [189] Dezfulian, 2007, Role of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics, Cardiovasc. Res. source
- Partly supportedcites [190] Webb, 2004, Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage, Proc. Natl. Acad. Sci. USA sourceExperimental — accuracy not yet measured
The Discussion reports that nitrite protects isolated rat hearts against ischemia–reperfusion injury, and the Methods show that infusion continued during ischemia. The paper mentions nitrite derived from dietary nitrate and discusses earlier feline studies, but it does not establish protection in many animal models or test a distinct preconditioning stage. Page numbers were not available in our copy. (LLM, conf=0.86)
- Partly supportedcites [191] Kumar, 2008, Chronic sodium nitrite therapy augments ischemia-induced angiogenesis and arteriogenesis, Proc. Natl. Acad. Sci. USA sourceExperimental — accuracy not yet measured
The Abstract (page unavailable) reports that sodium nitrite protects against acute ischemia/reperfusion injury in the heart and liver. The paper does not establish that nitrite is a dietary constituent or that it protects the heart across many animal models during both ischemia and preconditioning; its own experiment concerns murine hind-limb ischemia. (LLM, conf=0.87)
- Not checked yetcites [192] Lundberg, 2008, The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics, Nat. Rev. Drug Discov. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“These findings indicate that MOTS-c may act as an inhibitor of VCs via suppressing the expression of AT1 and ETB receptors, probably by activating AMPK signaling [136].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.4. Vascular Calcification (VC)
What the sources say
- Supportedcites [136] Wei, 2020, Mitochondrial-derived peptide MOTS-c attenuates vascular calcification and secondary myocardial remodeling via adenosine monophosphate-activated protein kinase signaling pathway, Cardiorenal. Med. source
The Conclusions state that MOTS-c attenuates vascular calcification by activating the AMPK pathway and reducing AT-1 and ET-B receptor expression. The Results report reduced receptor expression after MOTS-c treatment in the VDN rat model. Page numbers are not provided in our copy. (LLM, conf=0.94)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Supported
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In the paper
“These findings illustrating the results of AMPK activation, likely via downregulation of FUNDC1-related MAMs, represent a new therapeutic avenue for treating DCM [139].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Supportedcites [139] Wu, 2019, Hyperglycemia-Driven Inhibition of AMP-activated protein kinase alpha2 induces diabetic cardiomyopathy by promoting mitochondria-associated endoplasmic reticulum membranes in vivo, Circulation source
The Discussion (page not provided) explicitly identifies AMPK activation, likely through downregulation of FUNDC1 and FUNDC1-related MAMs, as a new therapeutic avenue for diabetic cardiomyopathy. The claim preserves the paper’s qualifier, “likely.” (LLM, conf=0.95)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Supported
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In the paper
“In Sprague Dawley rats, administration of pomegranate extract, composed of 40% punicalagin, effectively blocked HFD-induced cardiac accumulation of fat (e.g., cholesterol and triglycerides) and myocardial damage [142].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Supportedcites [142] Cao, 2015, Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation, Sci. Rep. source
The Abstract states that eight weeks of pomegranate extract containing 40% punicalagin prevented HFD-induced cardiac triglyceride and cholesterol accumulation and myocardial damage in male Sprague-Dawley rats. The Methods (Animals) confirm the rat strain and HFD-plus-extract treatment group. (LLM, conf=0.95)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pharmacological reagents, including statins, metformin, berberine, polyphenol, and resveratrol, all of which are widely used therapeutics for cardiovascular disorders, appear to deliver their protective/therapeutic effects partially via AMPK signaling modulation.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Binding of AMP, and to a lesser degree ADP, to the γ-subunit stimulates AMPK activity via three mechanisms [27,28,29].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [27] Hardie, 2011, AMP-activated protein kinase: Also regulated by ADP?, Trends Biochem. Sci. source
- Not checked yetcites [28] Gowans, 2013, AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation, Cell Metab. source
- Not checked yetcites [29] Ross, 2016, Differential regulation by AMP and ADP of AMPK complexes containing different gamma subunit isoforms, Biochem. J. source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Second, AMP protects Thr172 against dephosphorylation by phosphatases [28,35,36,37].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [28] Gowans, 2013, AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation, Cell Metab. source
- Not checked yetcites [35] Xiao, 2011, Structure of mammalian AMPK and its regulation by ADP, Nature source
- Not checked yetcites [36] Neumann, 2010, The PP1-R6 protein phosphatase holoenzyme is involved in the glucose-induced dephosphorylation and inactivation of AMP-activated protein kinase, a key regulator of insulin secretion, in MIN6 beta cells, FASEB J.
- Not checked yetcites [37] Joseph, 2015, Inhibition of AMP kinase by the protein phosphatase 2a heterotrimer, PP2APpp2r2d, J. Biol. Chem. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Once activated, AMPK redirects metabolism toward increased catabolism or decreased anabolism through the phosphorylation of key proteins across multiple pathways, including protein synthesis (e.g., mammalian target of rapamycin complex (1) [2,3], lipid homeostasis (e.g., acetyl coenzyme A carboxylase, ACC) [4,5], glucose metabolism (e.g., phosphofructokinase (2) [6], and mitochondrial homeostasis”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 1. Introduction
What the sources say
- Not checked yetcites [2] Gwinn, 2008, AMPK phosphorylation of raptor mediates a metabolic checkpoint, Mol. Cell source
- Not checked yetcites [3] Inoki, 2003, TSC2 mediates cellular energy response to control cell growth and survival, Cell source
- Not checked yetcites [4] Carling, 1987, A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis, FEBS Lett. source
- Not checked yetcites [5] Munday, 1988, Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase, Eur. J. Biochem. source
- Not checked yetcites [7] Jager, 2007, AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha, Proc. Natl. Acad. Sci. USA source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“AMPK is activated by energy stress and/or cellular stress in response to increased ATP consumption (e.g., exercise, cell proliferation, and anabolism) or decreased ATP production (e.g., low glucose levels, oxidative stress, and hypoxia), which are sensed as low ratios of ATP-to-AMP/ADP.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, activated AMPK balances energy levels by raising ATP synthesis and/or reducing ATP consumption.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 1. Introduction
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Third, AMP causes the allosteric activation of AMPK that has already been phosphorylated on Thr172.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Under conditions of insufficient energy, AMPK activates upon its binding with AMP or adenosine diphosphate (ADP) [1].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 1. Introduction
What the sources say
- Not checked yetcites [1] Hardie, 2012, AMPK: A nutrient and energy sensor that maintains energy homeostasis, Nat. Rev. Mol. Cell Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For instance, exposure of exogenous hydrogen peroxide to C2C12 cells led to a dose-dependent increase in AMPK activity by decreasing the ATP-to-ADP ratio [44].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [44] Hinchy, 2018, Mitochondria-derived ROS activate AMP-activated protein kinase (AMPK) indirectly, J. Biol. Chem. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The protective effects of fucoxanthin were attributed to activation of the AMPK-protein kinase C-NOX signaling pathway.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [129] Ou, 2019, Fucoxanthin protects against oxLDL-induced endothelial damage via activating the AMPK-Akt-CREB-PGC1alpha pathway, Mol. Nutr. Food Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Decreased NO bioavailability, manifested as impaired vasodilation, represents one of the early signs of atherosclerosis [154].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [154] Davignon, 2004, Role of endothelial dysfunction in atherosclerosis, Circulation source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The main mechanism relied on the stimulation of eNOS activation and NO production through the AMPK-dependent activation of the phosphatidylinositol-3-kinase- protein kinase B pathway [130].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [130] Xing, 2015, Salidroside improves endothelial function and alleviates atherosclerosis by activating a mitochondria-related AMPK/PI3K/Akt/eNOS pathway, Vascul. Pharmacol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Further, dominant negative mutation of LKB1 abolished both TPr agonists and hydrogen peroxide-stimulated AMPK activation, which suggested that hydrogen peroxide mediated TPr-triggered AMPK activation by LKB1 signaling [61].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [61] Zhang, 2008, Thromboxane receptor activates the AMP-activated protein kinase in vascular smooth muscle cells via hydrogen peroxide, Circ. Res. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Fucoxanthin, a natural marine carotenoid extracted from edible seaweeds, alleviated oxidative damage of ECs treated by oxLDL.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [129] Ou, 2019, Fucoxanthin protects against oxLDL-induced endothelial damage via activating the AMPK-Akt-CREB-PGC1alpha pathway, Mol. Nutr. Food Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Further, using HEK293 cells expressing AMPKγ2 R531G, an AMP-insensitive AMPK complex, AMPK cannot be activated by hydrogen peroxide [46].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [46] Hawley, 2010, Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation, Cell Metab. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“AMPK is activated by hydrogen peroxide in various cell types.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Exposure of cultured rat VSMCs to either TPr agonists or hydrogen peroxide led to AMPK activation in a time- and dose-dependent manner, as supported by the increased phosphor-AMPK at Thr172 and its downstream enzyme phosphor-ACC at Ser79 [61].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [61] Zhang, 2008, Thromboxane receptor activates the AMP-activated protein kinase in vascular smooth muscle cells via hydrogen peroxide, Circ. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Further evidence also shows that AMPK lies upstream of the phosphatidylinositol-3-kinase-protein kinase B pathway, which also leads to eNOS activation and NO production [162,164,165].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [162] Levine, 2007, Agonist-modulated regulation of AMP-activated protein kinase (AMPK) in endothelial cells. Evidence for an AMPK -> Rac1 -> Akt -> endothelial nitric-oxide synthase pathway, J. Biol. Chem. source
- Not checked yetcites [164] Ouchi, 2004, Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells, J. Biol. Chem. source
- Not checked yetcites [165] Nagata, 2003, AMP-activated protein kinase (AMPK) signaling in endothelial cells is essential for angiogenesis in response to hypoxic stress, J. Biol. Chem. source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“ROS, in excess, can provoke energy stress and metabolic failure by direct oxidizing and inactivating enzymes of the tricarboxylic acid cycle, electron transport chain (ETC), and glycolysis [62,63].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“AMPK is activated and in turn acts as a direct activator of eNOS by phosphorylating its Ser1177 residue [163].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [163] Chen, 2009, AMP-activated protein kinase functionally phosphorylates endothelial nitric oxide synthase Ser633, Circ. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Salidroside-induced AMPK activation was presumably related to the moderate depolarization of ΔΨm and subsequent increase of the cytosolic AMP-to-ATP ratio [130].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [130] Xing, 2015, Salidroside improves endothelial function and alleviates atherosclerosis by activating a mitochondria-related AMPK/PI3K/Akt/eNOS pathway, Vascul. Pharmacol. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings suggest that the target for hydrogen peroxide may not be AMPK itself, but components of the ETC, leading to a secondary effect on AMPK through changes to ADP, AMP, and ATP.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The addition of Trolox to mouse embryonic fibroblasts (MEFs) resulted in basal AMPK activity reduction, as evidenced by the decreased phosphor-AMPKα at Thr172 [51].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [51] Rabinovitch, 2017, AMPK maintains cellular metabolic homeostasis through regulation of mitochondrial reactive oxygen species, Cell Rep. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Salidroside, a phenylpropanoid glycoside isolated from the medicinal plant Rhodiola rosea, efficiently decreased atherosclerotic plaque formation in LDL receptor-deficient mice [130].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [130] Xing, 2015, Salidroside improves endothelial function and alleviates atherosclerosis by activating a mitochondria-related AMPK/PI3K/Akt/eNOS pathway, Vascul. Pharmacol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Obesity, diabetes mellitus, smoking, chronic kidney disease, and so on participate in the pathogenesis of atherosclerosis via a mechanism of changing NO bioavailability [153].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [153] Chen, 2018, Nitric oxide bioavailability dysfunction involves in atherosclerosis, Biomed. Pharmacother. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Esculetin has been reported to protect HUVEC against cytotoxicity after exposure of linoleic acid hydroperoxide, which is likely via its radical scavenging ability [166].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [166] Kaneko, 2001, Structure-activity relationship of antioxidants for inhibitors of linoleic acid hydroperoxide-induced toxicity in cultured human umbilical vein endothelial cells, Cytotechnology source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results collectively suggest that AMPK activation by hydrogen peroxide occurs through activation of either LKB1 or CaMKK, depending on the cell type.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Increasing evidence suggests that AMPK is essential in maintaining NO bioavailability.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [163] Chen, 2009, AMP-activated protein kinase functionally phosphorylates endothelial nitric oxide synthase Ser633, Circ. Res. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“Carvedilol modulates cardiac AMPK signaling to reduce ischemic insults by I/R [182].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [182] Hu, 2019, The cardioprotective effects of carvedilol on ischemia and reperfusion injury by AMPK signaling pathway, Biomed. Pharmacother. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Notably, the anti-atherogenic effects of mitochondria-targeted esculetin are likely owing to the promotion of mitochondrial biogenesis through AMPK–SIRT3 signaling [131].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [131] Karnewar, 2016, Mitochondria-targeted esculetin alleviates mitochondrial dysfunction by AMPK-mediated nitric oxide and SIRT3 regulation in endothelial cells: Potential implications in atherosclerosis, Sci. Rep. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In cultured human aortic endothelial cells, mechanistic study showed that mitochondria-targeted esculetin significantly inhibited angiotensin II-induced cell death via enhancement of NO production via AMPK–eNOS signaling [131].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [131] Karnewar, 2016, Mitochondria-targeted esculetin alleviates mitochondrial dysfunction by AMPK-mediated nitric oxide and SIRT3 regulation in endothelial cells: Potential implications in atherosclerosis, Sci. Rep. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Further, the impairment of tube formation in AMPKα1−/− or AMPKα2−/− cells could be normalized by adenoviral overexpression of UCP2 [132].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [132] Xu, 2011, Impaired expression of uncoupling protein 2 causes defective postischemic angiogenesis in mice deficient in AMP-activated protein kinase alpha subunits, Arterioscler. Thromb. Vasc. Biol. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“A growing body of evidence has indicated that AMPK activation shows a protective effect on cardiomyocytes under myocardial ischemic injury [170].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [170] Young, 2008, AMP-activated protein kinase conducts the ischemic stress response orchestra, Circulation source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“Recent studies suggest that the cardioprotective effects of metformin on I/R are mediated by its activation of AMPK.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [183] Calvert, 2008, Acute metformin therapy confers cardioprotection against myocardial infarction via AMPK-eNOS-mediated signaling, Diabetes source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“These findings provide important information that myocardial AMPK–eNOS activation by metformin following I/R led to cardioprotection [183].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [183] Calvert, 2008, Acute metformin therapy confers cardioprotection against myocardial infarction via AMPK-eNOS-mediated signaling, Diabetes source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“AMPK activation plays a crucial role in mitochondrial quality control under chronic hypoxia via modulating mitophagy in the heart [133].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [133] Zhang, 2018, AMPK activation serves a critical role in mitochondria quality control via modulating mitophagy in the heart under chronic hypoxia, Int. J. Mol. Med.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“I/R injury is primarily induced by endothelial cell apoptosis in microcirculation.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [179] Kloner, 1974, The “no-reflow” phenomenon after temporary coronary occlusion in the dog, J. Clin. Investig. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Study showed that inhibition of AMPK by either pharmacological inhibitor compound C or gene silencing significantly reduced tube formation in HUVECs [132].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [132] Xu, 2011, Impaired expression of uncoupling protein 2 causes defective postischemic angiogenesis in mice deficient in AMP-activated protein kinase alpha subunits, Arterioscler. Thromb. Vasc. Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Alternatively, administration of NO donor, sodium nitroprusside, restored the tube formation in both AMPKα1−/− and AMPKα2−/− mice [132].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [132] Xu, 2011, Impaired expression of uncoupling protein 2 causes defective postischemic angiogenesis in mice deficient in AMP-activated protein kinase alpha subunits, Arterioscler. Thromb. Vasc. Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Importantly, carvedilol treatment improved calcium homeostasis with rescuing the peak Ca2+ signal, the maximum rate of Ca2+ change during contraction and relaxation under hypoxia conditions [182].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [182] Hu, 2019, The cardioprotective effects of carvedilol on ischemia and reperfusion injury by AMPK signaling pathway, Biomed. Pharmacother. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Despite the successful revascularization of occluded vessels in the heart, reperfusion failure occurs in approximately 30% of patients with acute MI [177,178].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [177] Dauber, 1990, Functional coronary microvascular injury evident as increased permeability due to brief ischemia and reperfusion, Circ. Res. source
- Not checked yetcites [178] Weir, 2010, Microvascular obstruction remains a portent of adverse remodeling in optimally treated patients with left ventricular systolic dysfunction after acute myocardial infarction, Circ. Cardiovasc. Imaging source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Hypoxia activates AMPK through the ROS-mediated opening of calcium release-activated calcium channels [58,133].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [58] Mungai, 2011, Hypoxia triggers AMPK activation through reactive oxygen species-mediated activation of calcium release-activated calcium channels, Mol. Cell. Biol. source
- Not checked yetcites [133] Zhang, 2018, AMPK activation serves a critical role in mitochondria quality control via modulating mitophagy in the heart under chronic hypoxia, Int. J. Mol. Med.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Excessive mitochondrial fission aggravates cardiac I/R injury via alternating the balance of pro- and anti-survival factors [184].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [184] Ji, 2016, Aldehyde dehydrogenase 2 has cardioprotective effects on myocardial ischaemia/reperfusion injury via suppressing mitophagy, Front. Pharmacol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Recently, mitochondrial homeostasis has been attributed as a critical regulator of cell death during cardiac I/R injury, especially mitochondrial fission and mitophagy [184].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [184] Ji, 2016, Aldehyde dehydrogenase 2 has cardioprotective effects on myocardial ischaemia/reperfusion injury via suppressing mitophagy, Front. Pharmacol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The beneficial actions of metformin disappeared in cardiac-specific dominant-negative AMPKα2 transgenic mice or eNOS deficient mice [183].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [183] Calvert, 2008, Acute metformin therapy confers cardioprotection against myocardial infarction via AMPK-eNOS-mediated signaling, Diabetes source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In comparison with WT mice, the ischemia-induced ser1177 phosphorylation of eNOS in thigh adductor muscles was blocked in both AMPKα1−/− and AMPKα2−/− mice [132].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [132] Xu, 2011, Impaired expression of uncoupling protein 2 causes defective postischemic angiogenesis in mice deficient in AMP-activated protein kinase alpha subunits, Arterioscler. Thromb. Vasc. Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Administration of metformin before ischemia or at reperfusion decreased myocardial injury in mice [183].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [183] Calvert, 2008, Acute metformin therapy confers cardioprotection against myocardial infarction via AMPK-eNOS-mediated signaling, Diabetes source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“AMPK has been proven to be essential for ischemic angiogenesis; however, the mechanism by which AMPK promotes angiogenesis is poorly elucidated [165].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [165] Nagata, 2003, AMP-activated protein kinase (AMPK) signaling in endothelial cells is essential for angiogenesis in response to hypoxic stress, J. Biol. Chem. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Further, metformin failed to increase eNOS Ser1177 phosphorylation at reperfusion in AMPKα2 deficient mice [183].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [183] Calvert, 2008, Acute metformin therapy confers cardioprotection against myocardial infarction via AMPK-eNOS-mediated signaling, Diabetes source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Melatonin treatment reveals a protective role in cardiac microvasculature under I/R injury by activating AMPK [134].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [134] Zhou, 2017, Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis, J. Pineal. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Collectively, these results concluded that, in ECs, AMPK-dependent UCP2 expression together with eNOS phosphorylation promotes angiogenesis [132].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [132] Xu, 2011, Impaired expression of uncoupling protein 2 causes defective postischemic angiogenesis in mice deficient in AMP-activated protein kinase alpha subunits, Arterioscler. Thromb. Vasc. Biol. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Notably, AMPK agonist AICAR dramatically increased mitophagy [133].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [133] Zhang, 2018, AMPK activation serves a critical role in mitochondria quality control via modulating mitophagy in the heart under chronic hypoxia, Int. J. Mol. Med.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Supplementation of PK11195, a ligand of TSPO, markedly reduced neointima formation in carotid arteries after balloon injury, through the suppression of the phenotype switching of VSMC [137].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.5. Neointimal Hyperplasia Formation
What the sources say
- Not checked yetcites [137] Wu, 2020, TSPO ligands prevent the proliferation of vascular smooth muscle cells and attenuate neointima formation through AMPK activation, Acta Pharmacol. Sin. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The activation of AMPK signaling is required for the cardioprotective effect of nitrite in the preconditioning stage of I/R [135].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [135] Mo, 2014, Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion and tolerance to ischaemia/reperfusion, Cardiovasc. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Notably, in vivo animal study showed consistent results that nitrite protected the heart against I/R injury through the activation of protein kinase A [135].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [135] Mo, 2014, Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion and tolerance to ischaemia/reperfusion, Cardiovasc. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Study showed that MOTS-c treatment significantly attenuated VCs induced by vitamin D3 and nicotine [136].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.4. Vascular Calcification (VC)
What the sources say
- Not checked yetcites [136] Wei, 2020, Mitochondrial-derived peptide MOTS-c attenuates vascular calcification and secondary myocardial remodeling via adenosine monophosphate-activated protein kinase signaling pathway, Cardiorenal. Med. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In a model of balloon-injured carotid arteries, TSPO expression was dramatically increased in carotid arteries [136].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.5. Neointimal Hyperplasia Formation
What the sources say
- Not checked yetcites [136] Wei, 2020, Mitochondrial-derived peptide MOTS-c attenuates vascular calcification and secondary myocardial remodeling via adenosine monophosphate-activated protein kinase signaling pathway, Cardiorenal. Med. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The translocator protein (TSPO), an 18 kDa protein located at the outer mitochondrial membrane, is involved in the aberrant VSMC proliferation after angioplasty [137].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.5. Neointimal Hyperplasia Formation
What the sources say
- Not checked yetcites [137] Wu, 2020, TSPO ligands prevent the proliferation of vascular smooth muscle cells and attenuate neointima formation through AMPK activation, Acta Pharmacol. Sin. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In cultured rat H9c2 cardiomyoblasts treated with H/R, preconditioning with nitrite markedly attenuated cell death following hypoxia [135].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [135] Mo, 2014, Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion and tolerance to ischaemia/reperfusion, Cardiovasc. Res. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“An AMPK-specific inhibitor, compound C, abolished PK11195-induced inhibition of the proliferation and migration of platelet-derived growth factor-BB-treated A10 cells [137].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.5. Neointimal Hyperplasia Formation
What the sources say
- Not checked yetcites [137] Wu, 2020, TSPO ligands prevent the proliferation of vascular smooth muscle cells and attenuate neointima formation through AMPK activation, Acta Pharmacol. Sin. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Furthermore, it was found that PK11195 activated AMPK in A10 cells in a dose-dependent manner.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.5. Neointimal Hyperplasia Formation
What the sources say
- Not checked yetcites [137] Wu, 2020, TSPO ligands prevent the proliferation of vascular smooth muscle cells and attenuate neointima formation through AMPK activation, Acta Pharmacol. Sin. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“ETB and AT1 are reportedly involved in AMPK pathway by binding to their receptors [194,195].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.4. Vascular Calcification (VC)
What the sources say
- Not checked yetcites [194] Kim, 2017, Angiotensin II affects inflammation mechanisms via AMPK-related signalling pathways in HL-1 atrial myocytes, Sci. Rep. source
- Not checked yetcites [195] Chen, 2018, Homocysteine up-regulates ETB receptors via suppression of autophagy in vascular smooth muscle cells, Microvasc. Res. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Notably, all the beneficial effects of melatonin on microvasculature were abolished in AMPKα null mice [134].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [134] Zhou, 2017, Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis, J. Pineal. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Activation of AMPK by AICAR or metformin protects the heart from cardiac hypertrophy induced by aging and other stresses [202].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [202] Turdi, 2010, AMP-activated protein kinase deficiency exacerbates aging-induced myocardial contractile dysfunction, Aging Cell source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“Studies showed that AMPK deletion promoted mitochondrial fragmentation in ECs by inhibiting the autophagy-dependent degradation of DRP1 [105].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [105] Wang, 2017, Deletion of PRKAA triggers mitochondrial fission by inhibiting the autophagy-dependent degradation of DNM1L, Autophagy source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The most studied mechanism for mitophagy in mammalian cells is mediated by the cytoplasmic E3 ubiquitin ligase PARKIN [210] and the mitochondrial membrane kinase PINK1 [211].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“This phosphorylation proved critical for the efficient recruitment of PARKIN to mitochondria to initiate mitophagy during HF [117].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [117] Wang, 2018, AMPKalpha2 protects against the development of heart failure by enhancing mitophagy via pink1 phosphorylation, Circ. Res. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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In the paper
“In contrast, AMPKα2−/− mice showed an exacerbated progression of TAC-induced HF through defected cardiac mitophagy [117].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [117] Wang, 2018, AMPKalpha2 protects against the development of heart failure by enhancing mitophagy via pink1 phosphorylation, Circ. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“A line of evidence indicates that mitochondrial dynamics plays a pivotal role in endothelial dysfunction during macrovascular complications [220,221].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Additionally, mitochondria are a susceptible target of oxidative damage, which causes a malicious circle of events in ECs [224,225,226].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [224] Shigenaga, 1994, Oxidative damage and mitochondrial decay in aging, Proc. Natl. Acad. Sci. USA source
- Not checked yetcites [225] Green, 2004, Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes, Diabetes source
- Not checked yetcites [226] Brand, 2016, Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling, Free Radic. Biol. Med. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Further, ser495 in PINK1 underwent phosphorylation by AMPKα2 upon the dissipation of the ΔΨm in cardiomyocytes [117].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [117] Wang, 2018, AMPKalpha2 protects against the development of heart failure by enhancing mitophagy via pink1 phosphorylation, Circ. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Numerous anti-diabetic agents may improve endothelial function by targeting AMPK to impact mitochondrial dynamics [227].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [227] Lu, 2019, AMPK is associated with the beneficial effects of antidiabetic agents on cardiovascular diseases, Biosci. Rep. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“SIRT5, primarily localizing at the mitochondrial matrix, plays a vital role in mitochondrial function via increased mitochondrial nicotinamide adenine dinucleotide and ATP synthase activity [138].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [138] Zhang, M., Wu, J., Sun, R., Tao, X., Wang, X., Kang, Q., Wang, H., Zhang, L., Liu, P., and Zhang, J. (2019). SIRT5 deficiency suppresses mitochondrial ATP production and promotes AMPK activation in response to energy stress. PLoS ONE, 14. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Furthermore, AMPK deficiency also contributes to cardiac hypertrophy induced by aging, neurohumoral activation, pressure overload, and MI [201].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [201] Zaha, 2012, AMP-activated protein kinase regulation and biological actions in the heart, Circ. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In diabetes, mitochondrial dysfunction induces and aggravates macrovascular complications [218,219].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [218] Wang, 2017, Metformin suppresses diabetes-accelerated atherosclerosis via the inhibition of drp1-mediated mitochondrial fission, Diabetes source
- Not checked yetcites [219] Sorrentino, 2018, Repairing mitochondrial dysfunction in disease, Annu. Rev. Pharmacol. Toxicol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Recently, studies in pressure overload-induced cardiac hypertrophy and HF models highlight the role of AMPKα2 in the regulation of PINK1–PARKIN-dependent mitophagy [117].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [117] Wang, 2018, AMPKalpha2 protects against the development of heart failure by enhancing mitophagy via pink1 phosphorylation, Circ. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Accumulating evidence suggests that mitophagy impairment can induce cardiomyocyte death and HF [206,207,208,209].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [206] Tong, 2019, Mitophagy is essential for maintaining cardiac function during high fat diet-induced diabetic cardiomyopathy, Circ. Res. source
- Not checked yetcites [207] Cahill, 2016, Resistance of dynamin-related protein 1 oligomers to disassembly impairs mitophagy, resulting in myocardial inflammation and heart failure, J. Biol. Chem. source
- Not checked yetcites [208] Ikeda, 2015, Endogenous Drp1 mediates mitochondrial autophagy and protects the heart against energy stress, Circ. Res. source
- Not checked yetcites [209] Oka, 2012, Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure, Nature source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“The adenovirus overexpression of AMPKα2 in hearts blocked TAC-induced chronic HF via promoting mitophagy and mitochondrial function [117].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [117] Wang, 2018, AMPKalpha2 protects against the development of heart failure by enhancing mitophagy via pink1 phosphorylation, Circ. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In parallel, cardiac LKB1 null mice are associated with hypertrophy [200].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [200] Ikeda, 2009, Cardiac-specific deletion of LKB1 leads to hypertrophy and dysfunction, J. Biol. Chem. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“SIRT5, a member of the nicotinamide adenine dinucleotide-dependent sirtuin family of protein deacetylases, removes posttranslational modifications including malonylation, glutarylation, and succinylation on lysine residues [204,205].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Empagliflozin exerted its protective roles via inhibition of AMPK-dependent mitochondrial fission [229].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [229] Zhou, 2018, Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission, Redox Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“Empagliflozin recovered the AMP-to-ATP ratio that is necessary for triggering AMPK activation [229].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [229] Zhou, 2018, Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission, Redox Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“Endothelial dysfunction, the initial step of CVDs, is considered as a core modulator of vascular impairment in diabetes [215].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [215] Forbes, 2013, Mechanisms of diabetic complications, Physiol. Rev. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Additionally, AICAR, an AMPK activator, plays anti-inflammatory roles in vascular cells both in vitro and in vivo [248,249,250].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [248] Ewart, 2008, Inhibition of tumor necrosis factor alpha-stimulated monocyte adhesion to human aortic endothelial cells by AMP-activated protein kinase, Arterioscler. Thromb. Vasc. Biol. source
- Not checked yetcites [249] Zhang, 2011, AMP-activated protein kinase suppresses endothelial cell inflammation through phosphorylation of transcriptional coactivator p300, Arterioscler. Thromb. Vasc. Biol. source
- Not checked yetcites [250] Hawley, 2002, The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism, Diabetes source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“DRP1-dependent mitochondrial fission triggered mitochondrial apoptotic pathway, as shown by the caspase 9 cleavage, ΔΨm decline, cytochrome c leakage, as well as increased expression of proapoptotic proteins [140].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [140] Cui, 2018, Melatonin alleviates inflammation-induced apoptosis in human umbilical vein endothelial cells via suppression of Ca(2+)-XO-ROS-Drp1-mitochondrial fission axis by activation of AMPK/SERCA2a pathway, Cell Stress Chaperones source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Collectively, inflammation, NO bioavailability, insulin resistance, and oxLDL are the main participating factors in obesity-related endothelial dysfunction [261].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [261] Engin, 2017, Endothelial dysfunction in obesity, Adv. Exp. Med. Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“For instance, melatonin protected HUVECs against lipopolysaccharide-mediated apoptosis [140].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [140] Cui, 2018, Melatonin alleviates inflammation-induced apoptosis in human umbilical vein endothelial cells via suppression of Ca(2+)-XO-ROS-Drp1-mitochondrial fission axis by activation of AMPK/SERCA2a pathway, Cell Stress Chaperones source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Vascular inflammation stimulates the production of chemoattractants and molecules such as monocyte chemotactic proteins and vascular cell adhesion molecule 1 in endothelium [242,243,244].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [242] Marui, 1993, Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells, J. Clin. Investig. source
- Not checked yetcites [243] Murao, 2000, TNF-alpha stimulation of MCP-1 expression is mediated by the Akt/PKB signal transduction pathway in vascular endothelial cells, Biochem. Biophys. Res. Commun. source
- Not checked yetcites [244] Kirii, 2003, Lack of interleukin-1beta decreases the severity of atherosclerosis in ApoE-deficient mice, Arterioscler. Thromb. Vasc. Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Indeed, studies have uncovered that AMPK exerted its anti-inflammatory roles on the vasculature partially via the inhibition of adhesion molecules and chemoattractants [248,249,252,253] by regulating signal transducer and activator of transcription 3, of nuclear factor kappa B, and p300 pathways [254,255,256].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [248] Ewart, 2008, Inhibition of tumor necrosis factor alpha-stimulated monocyte adhesion to human aortic endothelial cells by AMP-activated protein kinase, Arterioscler. Thromb. Vasc. Biol. source
- Not checked yetcites [249] Zhang, 2011, AMP-activated protein kinase suppresses endothelial cell inflammation through phosphorylation of transcriptional coactivator p300, Arterioscler. Thromb. Vasc. Biol. source
- Not checked yetcites [252] Nerstedt, 2010, AMP-activated protein kinase inhibits IL-6-stimulated inflammatory response in human liver cells by suppressing phosphorylation of signal transducer and activator of transcription 3 (STAT3), Diabetologia source
- Not checked yetcites [253] Salminen, 2011, AMP-activated protein kinase inhibits NF-kappaB signaling and inflammation: Impact on healthspan and lifespan, J. Mol. Med. (Berl) source
- Not checked yetcites [254] Gongol, 2013, AMPKalpha2 exerts its anti-inflammatory effects through PARP-1 and Bcl-6, Proc. Natl. Acad. Sci. USA source
- Not checked yetcites [255] Hattori, 2006, Metformin inhibits cytokine-induced nuclear factor kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells, Hypertension source
- Not checked yetcites [256] Mancini, 2018, Canagliflozin inhibits interleukin-1beta-stimulated cytokine and chemokine secretion in vascular endothelial cells by AMP-activated protein kinase-dependent and -independent mechanisms, Sci. Rep. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“As discussed previously, a similar general outcome of metformin, AICAR, atheroprotective flow, and statins on ECs can be found through AMPK activation [245,250,251].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [245] Zhang, 2006, AMP-activated protein kinase is involved in endothelial NO synthase activation in response to shear stress, Arterioscler. Thromb. Vasc. Biol. source
- Not checked yetcites [250] Hawley, 2002, The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism, Diabetes source
- Not checked yetcites [251] Li, 2008, AMP-activated protein kinase promotes the differentiation of endothelial progenitor cells, Arterioscler. Thromb. Vasc. Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“FFAs also contribute to a higher production of ROS and inflammation in ECs [260].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [260] Inoguchi, 2000, High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C--dependent activation of NAD(P)H oxidase in cultured vascular cells, Diabetes source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Collectively, this study demonstrated that melatonin induced endothelial cell apoptosis through activation of the AMPK-sarcoplasmic/endoplasmic reticulum calcium ATPase 2a pathway under conditions of inflammation [140].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [140] Cui, 2018, Melatonin alleviates inflammation-induced apoptosis in human umbilical vein endothelial cells via suppression of Ca(2+)-XO-ROS-Drp1-mitochondrial fission axis by activation of AMPK/SERCA2a pathway, Cell Stress Chaperones source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In addition, AMPK activation reversed DCM by suppressing high glucose-induced MAM formation, mitochondrial Ca2+ increase, and mitochondrial dysfunction in cultured mouse neonatal cardiomyocytes 139].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [139] Wu, 2019, Hyperglycemia-Driven Inhibition of AMP-activated protein kinase alpha2 induces diabetic cardiomyopathy by promoting mitochondria-associated endoplasmic reticulum membranes in vivo, Circulation source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Recently, deep mechanistic studies into the cardiovascular protection of AMPK using endothelial or myelomonocytic cell-specific AMPK KO mice have revealed the potent anti-inflammatory properties of AMPK in hypertension [145].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [145] Jansen, T., Kvandová, M., Daiber, A., Stamm, P., Frenis, K., Schulz, E., Münzel, T., and Kröller-Schön, S. (2020). The AMP-activated protein kinase plays a role in antioxidant defense and regulation of vascular inflammation. Antioxidants (Basel), 9. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Metformin has been proven as an anti-inflammatory, especially for the inflammation in diabetes and following postsurgical endotoxin [245,246,247].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [245] Zhang, 2006, AMP-activated protein kinase is involved in endothelial NO synthase activation in response to shear stress, Arterioscler. Thromb. Vasc. Biol. source
- Not checked yetcites [246] Caballero, 2004, The differential effects of metformin on markers of endothelial activation and inflammation in subjects with impaired glucose tolerance: A placebo-controlled, randomized clinical trial, J. Clin. Endocrinol. Metab. source
- Not checked yetcites [247] Bergheim, 2006, Metformin prevents endotoxin-induced liver injury after partial hepatectomy, J. Pharmacol. Exp. Ther. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Cell culture study demonstrated that punicalagin was the main component of pomegranate extract that specifically activated AMPK in cardiomyocytes via quickly reducing the intracellular ATP-to-ADP ratio [142].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [142] Cao, 2015, Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation, Sci. Rep. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“A recent study of subjects with type 2 diabetes offered clear evidence of mitochondrial dysfunction in permeabilized right atrial cardiac fibers [271], suggesting improvement to mitochondrial function as a potential therapeutic strategy for obesity and its associated pathologies.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [271] Anderson, 2009, Substrate-specific derangements in mitochondrial metabolism and redox balance in the atrium of the type 2 diabetic human heart, J. Am. Coll. Cardiol. source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“CRA suppressed DRP1 activation by inducing DRP1 phosphorylation at Ser637, thus inhibiting mitochondrial fission in ECs in response to palmitate (PA) treatment [141].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [141] Li, 2016, Inhibition of mitochondrial fission and NOX2 expression prevent nlrp3 inflammasome activation in the endothelium: The role of corosolic acid action in the amelioration of endothelial dysfunction, Antioxid. Redox Signal. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Concurrently, CRA suppressed PA-induced NOX2 activation, which was revealed by the reduced migration of p47phox to cell membrane and inhibition of gp91phox expression [141].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [141] Li, 2016, Inhibition of mitochondrial fission and NOX2 expression prevent nlrp3 inflammasome activation in the endothelium: The role of corosolic acid action in the amelioration of endothelial dysfunction, Antioxid. Redox Signal. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“AMPK activity was observed to be suppressed by high-fat diet (HFD) in diverse tissues, including white heart, adipose tissue, and liver [266].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [266] Lindholm, 2013, A high-fat diet decreases AMPK activity in multiple tissues in the absence of hyperglycemia or systemic inflammation in rats, J. Physiol. Biochem. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Study showed that CRA alleviated endothelial inflammation in obesity by activating AMPK [141].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [141] Li, 2016, Inhibition of mitochondrial fission and NOX2 expression prevent nlrp3 inflammasome activation in the endothelium: The role of corosolic acid action in the amelioration of endothelial dysfunction, Antioxid. Redox Signal. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“These findings collectively elucidated that punicalagin, by activating AMPK, prevented HFD-related cardiac disorders via modulating mitochondria as well as phase II enzymes [142].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [142] Cao, 2015, Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation, Sci. Rep. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“HFD-induced AMPK deficiency contributed to the enhanced cardiomyocyte death in myocardial ischemia [267].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [267] Shao, 2014, A redox-dependent mechanism for regulation of AMPK activation by thioredoxin1 during energy starvation, Cell Metab. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 21
- It may state two separate claims as one. 71
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In humans, each subunit has multiple distinct isoforms encoded by different genes: the α-subunit has two isoforms, α1 and α2, encoded by gene PRKAA1 and PRKAA2, respectively [20]; the β-subunit has two isoforms, β1 and β2, encoded by gene PRKAB1 and PRKAB2, respectively [21]; and the γ-subunit has three isoforms, γ1, γ2, and γ3, encoded by gene PRKAG1, PRKAG2, and PRKAG3, respectively [22].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.1. AMPK Structure
What the sources say
- Not checked yetcites [20] Stapleton, 1996, Mammalian AMP-activated protein kinase subfamily, J. Biol. Chem. source
- Not checked yetcites [21] Thornton, 1998, Identification of a novel AMP-activated protein kinase beta subunit isoform that is highly expressed in skeletal muscle, J. Biol. Chem. source
- Partly supportedcites [22] Cheung, 2000, Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding, Biochem. J. sourceExperimental — accuracy not yet measured
The Discussion and the section on isolation of cDNA clones identify three human AMPK γ isoforms—γ1, γ2, and γ3—and describe distinct sequences encoding γ2 and γ3. Our copy does not give the gene names PRKAG1, PRKAG2, and PRKAG3 or explicitly assign each isoform to one of those genes. Citation [22] is attached to the γ-subunit clause, not the preceding α- and β-subunit clauses. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition to its conventional roles as an intracellular energy switch or fuel gauge, emerging research has shown that AMPK is also a redox sensor and modulator, playing pivotal roles in maintaining cardiovascular processes and inhibiting disease progression.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Activation loop phosphorylation increases AMPK activity by about 100-fold, while allosteric regulation changes AMPK activity up to tenfold in mammalian cells and about twofold in recombinant, bacterially produced AMPK [26,28,38,39].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [26] Xiao, 2007, Structural basis for AMP binding to mammalian AMP-activated protein kinase, Nature source
- Not checked yetcites [28] Gowans, 2013, AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation, Cell Metab. source
- Not checked yetcites [38] Sanders, 2007, Defining the mechanism of activation of AMP-activated protein kinase by the small molecule A-769662, a member of the thienopyridone family, J. Biol. Chem. source
- Not checked yetcites [39] Davies, 1995, 5’-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2AC, FEBS Lett. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“ROS are plenty of free radicals and chemically reactive molecules derived from oxygen molecule [41].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [41] Alfadda, 2012, Reactive oxygen species in health and disease, J. Biomed. Biotechnol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Accumulating studies have demonstrated crosstalk between AMPK and mitochondria, such as AMPK regulation of mitochondrial homeostasis and mitochondrial dysfunction causing abnormal AMPK activity.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
In the paper
“Each AMPK complex is comprised of an α-subunit, a β-subunit, and a γ-subunit, and all possible combinations produce 12 different AMPK complexes [23].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.1. AMPK Structure
What the sources say
- Not checked yetcites [23] Ross, 2016, AMP-activated protein kinase: A cellular energy sensor that comes in 12 flavours, FEBS J. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The γ-subunit allows AMPK to react to changes in the level of AMP, ADP, and ATP, as it includes four tandem cystathionine β synthase motifs that allow AMPK to bind adenine nucleotides [26].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.1. AMPK Structure
What the sources say
- Not checked yetcites [26] Xiao, 2007, Structural basis for AMP binding to mammalian AMP-activated protein kinase, Nature source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Excessive production of ROS, usually termed oxidative stress, are caused by increased production and/or insufficient presence of endogenous antioxidants [41].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [41] Alfadda, 2012, Reactive oxygen species in health and disease, J. Biomed. Biotechnol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Most ROS are generated as byproducts of mitochondrial electron transportation from the reduction of molecular oxygen to produce superoxide [41].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [41] Alfadda, 2012, Reactive oxygen species in health and disease, J. Biomed. Biotechnol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Oxidative stress is considered detrimental because of its damage to fats, deoxyribonucleic acid, and proteins in a cell, which can lead to numerous diseases such as diabetes, cancer, neurodegenerative disease, and cardiovascular disease (CVD) [41].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [41] Alfadda, 2012, Reactive oxygen species in health and disease, J. Biomed. Biotechnol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“AMPK, a heterotrimeric complex, is composed of a catalytic α-subunit and beta (β) and gamma (γ) regulatory subunits [19].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.1. AMPK Structure
What the sources say
- Not checked yetcites [19] Yan, Y., Zhou, X.E., Xu, H.E., and Melcher, K. (2018). Structure and physiological regulation of AMPK. Int. J. Mol. Sci., 19. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The β-subunit includes a carbohydrate-binding module that grants AMPK to bind to glycogen [25].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.1. AMPK Structure
What the sources say
- Not checked yetcites [25] Hudson, 2003, A novel domain in AMP-activated protein kinase causes glycogen storage bodies similar to those seen in hereditary cardiac arrhythmias, Curr. Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Lastly, allosteric AMPK activation can also occur in non-phosphorylated AMPK, with even higher fold activation than phosphorylated AMPK [40].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [40] Willows, 2017, Phosphorylation of AMPK by upstream kinases is required for activity in mammalian cells, Biochem. J. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The α-subunit is essential, and a double knockout (KO) of AMPKα1 and AMPKα2 in mice gives rise to embryonic lethality [24].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.1. AMPK Structure
What the sources say
- Not checked yetcites [24] Viollet, 2009, AMPK: Lessons from transgenic and knockout animals, Front. Biosci. (Landmark Ed.) source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The α-subunit contains the kinase domain and a critical residue (Thr174 in α1-subunit and Thr172 in α2-subunit, hereafter referred to as Thr172) that is phosphorylated by upstream kinases [1].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.1. AMPK Structure
What the sources say
- Not checked yetcites [1] Hardie, 2012, AMPK: A nutrient and energy sensor that maintains energy homeostasis, Nat. Rev. Mol. Cell Biol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Liver kinase B 1 (LKB1) [32] and calcium/calmodulin-dependent protein kinase kinase (CAMKK) 2 [33,34] can be employed as the two main mammalian upstream molecules that phosphorylate AMPK.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [32] Woods, 2003, LKB1 is the upstream kinase in the AMP-activated protein kinase cascade, Curr. Biol. source
- Not checked yetcites [33] Fujiwara, 2016, Differential AMP-activated Protein Kinase (AMPK) Recognition mechanism of Ca2+/calmodulin-dependent protein kinase kinase isoforms, J. Biol. Chem. source
- Not checked yetcites [34] Hawley, 2005, Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase, Cell Metab. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In H4IIEC3 cells, exogenous hydrogen peroxide transiently increased the level of phosphor-AMPK by LKB1 signaling, while exogenous hydrogen peroxide promoted AMPK phosphorylation in HeLa cells by CaMKK signaling [42].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [42] Liangpunsakul, 2008, Effect of ethanol on hydrogen peroxide-induced AMPK phosphorylation, Am. J. Physiol. Gastrointest. Liver Physiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“TPr agonists-activated AMPK was mediated by hydrogen peroxide, as demonstrated by the results showing overexpression of catalase (CAT) abolished Tpr agonists-induced AMPK activation [61].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [61] Zhang, 2008, Thromboxane receptor activates the AMP-activated protein kinase in vascular smooth muscle cells via hydrogen peroxide, Circ. Res. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Exogenous or glucose oxidase-generated hydrogen peroxide induced direct S-glutathionylation on the AMPKα subunit at Cys299 and Cys304, which contributes to AMPK activation [48].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [48] Zmijewski, 2010, Exposure to hydrogen peroxide induces oxidation and activation of AMP-activated protein kinase, J. Biol. Chem. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Its decrease occurs in response to lipid infiltration, oxidative stress, and inflammatory factors, which play a vital role in endothelial dysfunction [153].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [153] Chen, 2018, Nitric oxide bioavailability dysfunction involves in atherosclerosis, Biomed. Pharmacother. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Additional evidence supporting AMPK protection against oxidative stress is that AMPK negatively regulates NOX by reducing its phosphorylation and preventing P47phox’s translocation to membrane [70,151].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [70] Wang, 2010, AMPKalpha2 deletion causes aberrant expression and activation of NAD(P)H oxidase and consequent endothelial dysfunction in vivo: Role of 26S proteasomes, Circ. Res. source
- Not checked yetcites [151] McCarty, 2009, AMP-activated kinase may suppress NADPH oxidase activation in vascular tissues, Med. Hypotheses source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, the suppression of oxidative stress, in turn, blunted the activation of the protein kinase B-cyclic AMP-responsive element binding protein–PGC1α pathway, which ameliorated mitochondrial dysfunction and apoptosis [129].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [129] Ou, 2019, Fucoxanthin protects against oxLDL-induced endothelial damage via activating the AMPK-Akt-CREB-PGC1alpha pathway, Mol. Nutr. Food Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Alternatively, some studies showed that ROS directly activated AMPK independent of changes in ADP, AMP, and ATP.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“AMPK suppresses protein kinase C activity and prevents protein kinase C modulation of p47phox phosphorylation [152].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [152] Ou, 2013, Ginkgo biloba extract attenuates oxLDL-induced endothelial dysfunction via an AMPK-dependent mechanism, J. Appl. Physiol. (1985) source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is well established that the ROS-induced energy stress strongly activates AMPK, which is likely the main mechanism of ROS-mediated AMPK activation.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Similarly, in NIH-3T3 cells, exogenous hydrogen peroxide transiently activated AMPK in a dose-dependent manner, which was associated with an increased AMP-to-ATP ratio [45].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 2. AMPK Structure and Regulation > 2.2. Regulation of AMPK
What the sources say
- Not checked yetcites [45] Choi, 2001, The regulation of AMP-activated protein kinase by H(2)O(2), Biochem. Biophys. Res. Commun. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Vasculature I/R injury alleviates the efficiency of reperfusion therapy and compromises the clinical benefits of patients with acute MI [181].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [181] Ndrepepa, 2010, 5-year prognostic value of no-reflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction, J. Am. Coll. Cardiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, with increasing mitochondria, the level of ROS is also increased as mitochondrial byproducts, which can result in oxidative damage of mitochondria [176].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [176] Fischer, 2012, Mitochondrial quality control: An integrated network of pathways, Trends Biochem. Sci. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Mitochondria-targeted esculetin, capable of scavenging mitochondrial ROS, greatly alleviated angiotensin II-induced monocyte infiltration, atherosclerotic plaque formation, and serum pro-inflammatory cytokine production in apolipoprotein E KO mice [131].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.1. Atherosclerosis
What the sources say
- Not checked yetcites [131] Karnewar, 2016, Mitochondria-targeted esculetin alleviates mitochondrial dysfunction by AMPK-mediated nitric oxide and SIRT3 regulation in endothelial cells: Potential implications in atherosclerosis, Sci. Rep. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“During early reperfusion, treatment with metformin augmented I/R-induced AMPK activation and significantly increased eNOS phosphorylation at ser1177 [183].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [183] Calvert, 2008, Acute metformin therapy confers cardioprotection against myocardial infarction via AMPK-eNOS-mediated signaling, Diabetes source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The apoptosis induces endothelial swelling, microvascular spasms, and capillary obstruction, which slows or even stops microcirculation blood flow following reperfusion [179].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [179] Kloner, 1974, The “no-reflow” phenomenon after temporary coronary occlusion in the dog, J. Clin. Investig. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These results suggest that AMPK participates in mitophagy regulation, which thereby provides a valuable therapeutic target for ischemic heart diseases.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [133] Zhang, 2018, AMPK activation serves a critical role in mitochondria quality control via modulating mitophagy in the heart under chronic hypoxia, Int. J. Mol. Med.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Similarly, in comparison with the WT cells, tube formation in mouse arterial endothelial cells isolated from either AMPKα1−/− or AMPKα2−/− mice was significantly impaired, exhibiting oxidative stress and reduced expression of UCP2.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [132] Xu, 2011, Impaired expression of uncoupling protein 2 causes defective postischemic angiogenesis in mice deficient in AMP-activated protein kinase alpha subunits, Arterioscler. Thromb. Vasc. Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Mitophagy increased significantly in cardiomyocytes exposed to hypoxic conditions, which was accompanied by AMPK activation [133].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [133] Zhang, 2018, AMPK activation serves a critical role in mitochondria quality control via modulating mitophagy in the heart under chronic hypoxia, Int. J. Mol. Med.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Under chronic hypoxia, PGC1α is upregulated, resulting in a subsequent increase of mitochondrial biogenesis [175].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [175] Zhu, 2010, Hypoxia induces PGC-1alpha expression and mitochondrial biogenesis in the myocardium of TOF patients, Cell Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Treatment of cardiomyocytes with carvedilol augmented phosphorylation of AMPK and its downstream substrate ACC, and ameliorated hypoxia-induced impairment [182].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [182] Hu, 2019, The cardioprotective effects of carvedilol on ischemia and reperfusion injury by AMPK signaling pathway, Biomed. Pharmacother. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mechanically, AMPK increased glucose uptake and glucose transporter 4 translocation [171], decreased apoptosis, improved post-ischemic recovery, and limited myocardial infarction (MI) [172,173].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [172] Ma, 2010, Impaired macrophage migration inhibitory factor-AMP-activated protein kinase activation and ischemic recovery in the senescent heart, Circulation source
- Not checked yetcites [173] Russell, 2004, AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury, J. Clin. Investig. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Consistently, when AMPK activation was blocked, mitophagy decreased as well, which subsequently gave rise to cardiomyocyte apoptosis [133].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [133] Zhang, 2018, AMPK activation serves a critical role in mitochondria quality control via modulating mitophagy in the heart under chronic hypoxia, Int. J. Mol. Med.
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“I/R injury causes myocardial damage and increases 30-day mortality rates [180].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [180] Abbate, 2008, No-reflow: The next challenge in treatment of ST-elevation acute myocardial infarction, Eur. Heart J. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Mechanically, AMPK increased glucose uptake and glucose transporter 4 translocation [171], decreased apoptosis, improved post-ischemic recovery, and limited myocardial infarction (MI) [172,173].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.2. Ischemia
What the sources say
- Not checked yetcites [171] Miller, 2008, Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart, Nature source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In vitro mechanism studies showed that I/R triggered a DRP1-dependent mitochondrial fragmentation, which subsequently led to oligomerization of voltage-dependent anion channel 1, liberation of hexokinase 2, opening of mitochondrial permeability transition pore, upregulation of PINK1–PARKIN signaling, and eventual mitophagy-mediated cell death [134].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [134] Zhou, 2017, Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis, J. Pineal. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is a bioactive mitochondrial-derived peptide shown to activate the AMPK pathway and modulate metabolic homeostasis [193].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.4. Vascular Calcification (VC)
What the sources say
- Not checked yetcites [193] Lee, 2015, The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance, Cell Metab. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Further mechanism studies showed that nitrite activated protein kinase A, which in turn suppressed DRP1-dependent mitochondrial fission, augmented ΔΨm, and promoted superoxide production [135].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [135] Mo, 2014, Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion and tolerance to ischaemia/reperfusion, Cardiovasc. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Melatonin promoted cell survival via AMPKα activation, accompanied by phosphor-DRP1-S616 reduction and phosphor-DRP1-S637 elevation, which normalized mitochondrial fission [134].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [134] Zhou, 2017, Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis, J. Pineal. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Melatonin significantly decreased myocadiac infarction, improved cardiac function, normalized blood flow, and lowered microcirculation perfusion impairment [134].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [134] Zhou, 2017, Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis, J. Pineal. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Histological analysis revealed that administration of melatonin restored the endothelial barrier, promoted eNOS expression, decreased inflammatory cell infiltration, and lowered endothelial damage in cardiac microcirculation endothelial cells [134].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [134] Zhou, 2017, Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis, J. Pineal. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“In parallel, phosphorylated AMPK increased and the expression of endothelin B (ETB) and angiotensin II receptor type 1 (AT1) receptors decreased after MOTS-c treatment [136].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.4. Vascular Calcification (VC)
What the sources say
- Not checked yetcites [136] Wei, 2020, Mitochondrial-derived peptide MOTS-c attenuates vascular calcification and secondary myocardial remodeling via adenosine monophosphate-activated protein kinase signaling pathway, Cardiorenal. Med. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“These results indicate that TSPO regulates neointimal formation after vascular injury via stimulating VSMC proliferation and migration, which is likely dependent on AMPK suppression [137].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.5. Neointimal Hyperplasia Formation
What the sources say
- Not checked yetcites [137] Wu, 2020, TSPO ligands prevent the proliferation of vascular smooth muscle cells and attenuate neointima formation through AMPK activation, Acta Pharmacol. Sin. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Neointimal hyperplasia narrows the luminal diameter, leading to decreased blood flow and recurrence of anginal symptoms [196].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.5. Neointimal Hyperplasia Formation
What the sources say
- Not checked yetcites [196] Schwartz, 1997, Perspectives series: Cell adhesion in vascular biology. Smooth muscle migration in atherosclerosis and restenosis, J. Clin. Investig. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“The prevention of mitochondrial fission further restored the interaction between voltage-dependent anion channel 1 and hexokinase 2, stopped mitochondrial permeability transition pore opening, and PINK1–PARKIN activation, ultimately blunting cell death [134].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [134] Zhou, 2017, Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis, J. Pineal. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The loss of AMPK activity is believed to be pro-hypertrophic because lines of molecular signaling pathways that control cell growth are attenuated by AMPK activation [197,198,199].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [197] Chan, 2008, Resveratrol inhibits cardiac hypertrophy via AMP-activated protein kinase and Akt, J. Biol. Chem. source
- Not checked yetcites [198] Chan, 2004, Activation of AMP-activated protein kinase inhibits protein synthesis associated with hypertrophy in the cardiac myocyte, J. Biol. Chem. source
- Not checked yetcites [199] Browne, 2004, Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398, J. Biol. Chem. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moreover, ROS scavenging blocks AMPK activation and blunts nitrite-induced cardioprotection after H/R [135].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.3. I/R
What the sources say
- Not checked yetcites [135] Mo, 2014, Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion and tolerance to ischaemia/reperfusion, Cardiovasc. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In the meantime, DRP1-S616 phosphorylation was decreased, while DRP1-S637 phosphorylation was increased, ultimately leading to mitochondrial fission [229].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [229] Zhou, 2018, Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission, Redox Biol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“However, some pharmacological AMPK activators, such as MK-8722 [203], cause cardiac hypertrophy, which is considered the main side effect of pharmacological pan-AMPK activation [17].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [203] Feng, 2018, Discovery of MK-8722: A systemic, direct pan-activator of amp-activated protein kinase, ACS Med. Chem. Lett. source
- Not checked yetcites [17] Myers, 2017, Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiac hypertrophy, Science source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“In failing heart samples from patients or TAC mice, the isoform of AMPKα shifted from α2 to α1, which is associated with reduced mitophagy and dysfunctional mitochondria [117].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [117] Wang, 2018, AMPKalpha2 protects against the development of heart failure by enhancing mitophagy via pink1 phosphorylation, Circ. Res. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Clusterin, which exerts beneficial effects in ECs under diabetic conditions (both type 1 and type 2), inhibits mitochondrial fragmentation while activating AMPK [228].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [228] Ren, 2019, Clusterin ameliorates endothelial dysfunction in diabetes by suppressing mitochondrial fragmentation, Free Radic. Biol. Med. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Consistently, SIRT5 ablation attenuated cardiac hypertrophy and cardiac dysfunction in the TAC model, which is accompanied by the reduction of ATP, increase of AMP-to-ATP ratio, and enhancement of AMPK activity [138].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [138] Zhang, M., Wu, J., Sun, R., Tao, X., Wang, X., Kang, Q., Wang, H., Zhang, L., Liu, P., and Zhang, J. (2019). SIRT5 deficiency suppresses mitochondrial ATP production and promotes AMPK activation in response to energy stress. PLoS ONE, 14. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Endothelial dysfunction is attributed to many causes, including oxidative stress, chronic inflammation, and endothelium activation, in diabetes, which exhibits excessive free fatty acid (FFA), insulin resistance, and/or hyperglycemia [216,217].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [216] Zhang, 2012, The link between metabolic abnormalities and endothelial dysfunction in type 2 diabetes: An update, Basic Res. Cardiol. source
- Not checked yetcites [217] Kim, 2006, Reciprocal relationships between insulin resistance and endothelial dysfunction: Molecular and pathophysiological mechanisms, Circulation source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“SIRT5 deficiency attenuated ATP production from mitochondrial ETC, increased the AMP-to-ATP ratio, and in turn activated AMPK in both cultured cells and hearts under the conditions of energy stress [138].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [138] Zhang, M., Wu, J., Sun, R., Tao, X., Wang, X., Kang, Q., Wang, H., Zhang, L., Liu, P., and Zhang, J. (2019). SIRT5 deficiency suppresses mitochondrial ATP production and promotes AMPK activation in response to energy stress. PLoS ONE, 14. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Both the conditions of hyperlipidemia and hyperglycemia impair mitochondrial dynamics by shifting the balance to excessive mitochondrial fission, leading to mitochondrial ROS over production and ETC impairment [221,222,223].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [221] LaRocca, 2014, Mitochondria-targeted antioxidant (MitoQ) ameliorates age-related arterial endothelial dysfunction in mice, J. Physiol. source
- Not checked yetcites [222] Huang, 2018, The uremic toxin hippurate promotes endothelial dysfunction via the activation of Drp1-mediated mitochondrial fission, Redox Biol. source
- Not checked yetcites [223] Yu, 2006, Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology, Proc. Natl. Acad. Sci. USA source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Thus, this study unveils a crucial role of SIRT5 in controlling cellular energy metabolism by AMPK activation upon energy stress, which further confirms the cardioprotective role of AMPK in left ventricular hypertrophy under the stress of pressure overload [138].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 5. AMPK, Mitochondrial Function, and CVDs > 5.6. Cardiac Hypertrophy
What the sources say
- Not checked yetcites [138] Zhang, M., Wu, J., Sun, R., Tao, X., Wang, X., Kang, Q., Wang, H., Zhang, L., Liu, P., and Zhang, J. (2019). SIRT5 deficiency suppresses mitochondrial ATP production and promotes AMPK activation in response to energy stress. PLoS ONE, 14. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“MAMs play a vital role in lipid transport, Ca2+ signaling, cell survival, and energy metabolism [234], and have been implicated in diseases including Alzheimer’s disease [235], cancer [236], lysosomal storage disease [237], diabetes mellitus [238,239], obesity, and metabolic disorders [240].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [234] Rowland, 2012, Endoplasmic reticulum-mitochondria contacts: Function of the junction, Nat. Rev. Mol. Cell Biol. source
- Not checked yetcites [235] Suski, 2017, Localization and processing of the amyloid-beta protein precursor in mitochondria-associated membranes, J. Alzheimers Dis.
- Not checked yetcites [236] Ando, 2018, Remodeling of Ca(2+) signaling in cancer: Regulation of inositol 1,4,5-trisphosphate receptors through oncogenes and tumor suppressors, Adv. Biol. Regul. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“High glucose-driven inactivation of AMPK increased FUNDC1, resulting in aberrant MAM formation, mitochondrial Ca2+ increase, mitochondrial dysfunction, and cardiac dysfunction [139].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [139] Wu, 2019, Hyperglycemia-Driven Inhibition of AMP-activated protein kinase alpha2 induces diabetic cardiomyopathy by promoting mitochondria-associated endoplasmic reticulum membranes in vivo, Circulation source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Upregulation of XO was accompanied by excessive ROS production, resulting in the Ser616 phosphorylation as well as the mitochondrial migration of DRP1 [140].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [140] Cui, 2018, Melatonin alleviates inflammation-induced apoptosis in human umbilical vein endothelial cells via suppression of Ca(2+)-XO-ROS-Drp1-mitochondrial fission axis by activation of AMPK/SERCA2a pathway, Cell Stress Chaperones source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Vildagliptin improved mitochondrial dysfunction in diabetic ECs, possibly by blunting DRP1-dependent mitochondrial fission by inducing AMPK activation [230].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [230] Liu, 2019, Vildagliptin improves high glucose-induced endothelial mitochondrial dysfunction via inhibiting mitochondrial fission, J. Cell. Mol. Med. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Thus, under diabetic conditions, ECs often have reduced eNOS activity and diminished NO production [259].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [259] Dresner, 1999, Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity, J. Clin. Investig. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Importantly, melatonin activated AMPK, which was associated with the upregulation of sarcoplasmic/endoplasmic reticulum calcium ATPase 2a [140].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [140] Cui, 2018, Melatonin alleviates inflammation-induced apoptosis in human umbilical vein endothelial cells via suppression of Ca(2+)-XO-ROS-Drp1-mitochondrial fission axis by activation of AMPK/SERCA2a pathway, Cell Stress Chaperones source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Obesity-related type 2 diabetes patients often have elevated plasma FFAs, because of either increased amounts of FFAs released from large amounts of adipose tissue or impaired FFA clearance [258].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [258] Boden, 2003, Effects of free fatty acids (FFA) on glucose metabolism: Significance for insulin resistance and type 2 diabetes, Exp. Clin. Endocrinol. Diabetes source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Further, melatonin-activated AMPK-sarcoplasmic/endoplasmic reticulum calcium ATPase 2a axis prevented calcium overload, XO-dependent ROS overproduction, DRP1-mediated mitochondrial fission, and apoptosis in lipopolysaccharide-treated cells [140].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [140] Cui, 2018, Melatonin alleviates inflammation-induced apoptosis in human umbilical vein endothelial cells via suppression of Ca(2+)-XO-ROS-Drp1-mitochondrial fission axis by activation of AMPK/SERCA2a pathway, Cell Stress Chaperones source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Lipopolysaccharide triggered cytosolic calcium overload, and in turn upregulated XO, whose activity is calcium-dependent [140].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
What the sources say
- Not checked yetcites [140] Cui, 2018, Melatonin alleviates inflammation-induced apoptosis in human umbilical vein endothelial cells via suppression of Ca(2+)-XO-ROS-Drp1-mitochondrial fission axis by activation of AMPK/SERCA2a pathway, Cell Stress Chaperones source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Study showed that mitochondrial outer membrane protein FUN14 domain containing 1 (FUNDC1) is essential for maintaining the MAM structure and ensuring appropriate Ca2+ transfer from the sarcoplasmic reticulum (i.e., ER in myocytes) to mitochondria in healthy hearts [241].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
What the sources say
- Not checked yetcites [241] Wu, 2017, Binding of FUN14 domain containing 1 with inositol 1,4,5-trisphosphate receptor in mitochondria-associated endoplasmic reticulum membranes maintains mitochondrial dynamics and function in hearts in vivo, Circulation source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“CRA activated AMPK in a LKB1-dependent manner, and AMPK silencing abrogated its inhibitory effect on DRP1 activation and mitochondrial fission [141].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [141] Li, 2016, Inhibition of mitochondrial fission and NOX2 expression prevent nlrp3 inflammasome activation in the endothelium: The role of corosolic acid action in the amelioration of endothelial dysfunction, Antioxid. Redox Signal. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“DRP1 knockdown attenuated PA-induced NOX2 activation, and knockdown of DRP1 or NOX2 suppressed PA-induced NACHT, LRR, and PYD domains-containing protein 3 inflammatory effect and, in the meantime, strengthened the inhibitory effects of CRA [141].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [141] Li, 2016, Inhibition of mitochondrial fission and NOX2 expression prevent nlrp3 inflammasome activation in the endothelium: The role of corosolic acid action in the amelioration of endothelial dysfunction, Antioxid. Redox Signal. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Obesity is closely associated with cardiac disorders, which is assumed to be a consequence of the adaption to an oversupply of high-fat substrates [262,263].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is well-accepted that AMPK activation plays protective roles across diverse CVDs.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 7. Perspectives
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“These data collectively demonstrated that CRA prevented mitochondrial fission by regulating DRP1 phosphorylation at Ser637 in an AMPK-dependent manner, contributing to the blockage of NOX2-related oxidative stress and suppressing NACHT, LRR, and PYD domains-containing protein 3 inflammasome in the endothelium [141].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [141] Li, 2016, Inhibition of mitochondrial fission and NOX2 expression prevent nlrp3 inflammasome activation in the endothelium: The role of corosolic acid action in the amelioration of endothelial dysfunction, Antioxid. Redox Signal. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Far beyond our current knowledge are the structural and functional changes to mitochondria that may be amplified under disease conditions.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 7. Perspectives
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AMPK has emerged as a guardian of mitochondria because almost all mitochondrial insults can activate AMPK.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 7. Perspectives
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, the interplay within the AMPK–mitochondrial axis during the initiation and progression of CVDs is poorly investigated.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 7. Perspectives
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Concomitantly, pomegranate extract activated AMPK, which may be responsible for the intervention of mitochondrial loss through promoting mitochondrial biogenesis and the attenuation of oxidative stress by means of upregulating phase II enzymes in HFD hearts [142].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [142] Cao, 2015, Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation, Sci. Rep. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“A direct functional connection between AMPK signaling and β-adrenergic responsiveness exists in the heart, and AMPK might be a valuable target to recover the decreased β-adrenergic responsive in the heart of obesity [270].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [270] Bussey, 2018, Cardiac beta-adrenergic responsiveness of obese Zucker rats: The role of AMPK, Exp. Physiol. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Limited evidence has focused on mitochondrial dynamics, mitochondrial biogenesis, and mitophagy, the three common functions of mitochondria that have been studied by cell biologists.”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 7. Perspectives
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Punicalagin, the major active component in pomegranate extract, protects against HFD-induced cardiac disorders by activating AMPK pathway and promoting mitochondrial biogenesis [142].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [142] Cao, 2015, Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation, Sci. Rep. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The loss of AMPK activity exacerbated cardiac hypertrophy and dysfunctional contractility of HFD-fed mice [268].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [268] Turdi, 2011, Deficiency in AMP-activated protein kinase exaggerates high fat diet-induced cardiac hypertrophy and contractile dysfunction, J. Mol. Cell. Cardiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“C1q/tumor necrosis factor-related protein 9 exhibited anti-myocardial lipotoxicity effects and attenuated cardiac hypertrophy, likely via activation of the LKB1–AMPK signaling [269].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [269] Zuo, 2020, CTRP9 knockout exaggerates lipotoxicity in cardiac myocytes and high-fat diet-induced cardiac hypertrophy through inhibiting the LKB1/AMPK pathway, J. Cell. Mol. Med. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Increased body weight switches the substrate of the heart from fatty acid to sugar, resulting in fat accumulation around the heart and eventually inducing cardiac impairment and increasing the risk of MI [264,265].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.3. Obesity
What the sources say
- Not checked yetcites [264] Schram, 2008, Implications of myocardial matrix remodeling by adipokines in obesity-related heart failure, Trends Cardiovasc. Med. source
- Not checked yetcites [265] Look, 2009, Adipocyte fatty acid-binding protein suppresses cardiomyocyte contraction: A new link between obesity and heart disease, Circ. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Mitochondria are the primary source of ATP production in the cell.
“Mitochondria are considered the primary source of ATP production in the cell.”
The paper relies on this without support.
Mitochondrial dysfunction occurs in the development of many cardiovascular diseases owing to production of ROS beyond control.
“Mitochondrial dysfunction occurs in the development of many CVDs such as atherosclerosis, ischemia-reperfusion (I/R) injury, hypertension, diabetes, cardiac hypertrophy, and heart failure (HF), owing to the production of ROS beyond control.”
The paper relies on this without support.
AMPK is widely expressed in the cardiovascular system.
“AMPK is widely expressed in the cardiovascular system.”
The paper relies on this without support.
The α1 isoform predominates in VSMCs, ECs, adipocytes, and monocytes/macrophages, whereas cardiomyocytes express much higher amounts of the α2 isoform.
“The α1 isoform predominates in VSMCs, ECs, adipocytes, and monocytes/macrophages, whereas cardiomyocytes express much higher amounts of the α2 isoform.”
The paper relies on this without support.
Aberrant AMPK signaling is involved in the pathogenesis of various cardiovascular diseases, including hypertension, atherosclerosis, and stroke.
“Moreover, aberrant AMPK signaling is involved in the pathogenesis of various CVDs, including hypertension, atherosclerosis, and stroke.”
The paper relies on this without support.
Oxidative stress caused by risk factors represents a major contributor to endothelial dysfunction as a common predisposing condition to atherosclerosis.
“Oxidative stress caused by risk factors represents a major contributor to endothelial dysfunction as a common predisposing condition to atherosclerosis.”
The paper relies on this without support.
UCP2 appears to have a main function of controlling ROS generation in diabetes, obesity, and atherosclerosis.
“It appears that UCP2 has a main function of controlling ROS generation in diabetes, obesity, and atherosclerosis, although it was originally considered as a modulator of nonshivering thermogenesis.”
The paper relies on this without support.
Rapid Ca2+ influx into mitochondrial matrix occurs through the mitochondrial Ca2+ uniporter, a specific channel located at the inner mitochondrial membrane.
“It is well established that rapid Ca2+ influx into mitochondrial matrix occurs through the mitochondrial Ca2+ uniporter (MCU), a specific channel located at the inner mitochondrial membrane.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For example, AMPK activators such as metformin and berberine improve mitochondrial efficiency and energy substrate utilization, which can reduce fatigue and increase endurance capacity”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [106]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For example, metformin and berberine activate AMPK, promoting fatty acid oxidation, mitochondrial biogenesis, and improved insulin sensitivity”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [106]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
“Empagliflozin exerted its protective roles via inhibition of AMPK-dependent mitochondrial fission [229].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.1. Diabetes
“In the meantime, DRP1-S616 phosphorylation was decreased, while DRP1-S637 phosphorylation was increased, ultimately leading to mitochondrial fission [229].”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
“For instance, melatonin protected HUVECs against lipopolysaccharide-mediated apoptosis [140].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 6. Cardio-Metabolic Diseases > 6.2. Inflammation
“Collectively, this study demonstrated that melatonin induced endothelial cell apoptosis through activation of the AMPK-sarcoplasmic/endoplasmic reticulum calcium ATPase 2a pathway under conditions of inflammation [140].”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 4. AMPK Regulates Mitochondrial Homeostasis > 4.2. AMPK Regulates Mitochondrial Dynamics
“In human bone osteosarcoma epithelial cells (U2OS) and MEFs, AMPK directly phosphorylated MFF on two sites, Ser155 and Ser173 [82,104].”
§ AMPK, Mitochondrial Function, and Cardiovascular Disease > 4. AMPK Regulates Mitochondrial Homeostasis > 4.2. AMPK Regulates Mitochondrial Dynamics
“A further study showed that AMPK-driven MFF phosphorylation at Ser155 and Ser172 is one potential mechanism to account for mitochondrial fission owing to mitochondrial respiration decline [82].”
Citations
Cites
5 retracted
Activation of the AMP-activated Protein Kinase by the Anti-diabetic Drug Metformin in Vivo
Zou, M., Kirkpatrick, S. S., Davis, B. J., Nelson, J. S., Wiles, W. G., Schlattner, U., Neumann, D., Brownlee, M., Freeman, M. B., & Goldman, M. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404421200 · Cited by 480
Self-citationRetractedXie, Z., Zhang, J., Wu, J., Viollet, B., & Zou, M. (2008) · Diabetes · doi:10.2337/db08-0610 · Cited by 165
Self-citationRetractedZhang, J., Xie, Z., Dong, Y., Wang, S., Liu, C., & Zou, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802578200 · Cited by 114
Self-citationRetractedRETRACTED: Redox Regulation of the AMP-Activated Protein Kinase
Han, Y., Wang, Q., Song, P., Zhu, Y., & Zou, M.-H. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015420 · Cited by 71
Self-citationRetractedZou, M.-H., Hou, X., Shi, C., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.w119.011600 · Cited by 2
Self-citationRetractedJames, S. L., Abate, D., Abate, K. H., Abay, S. M., Abbafati, C., Abbasi, N., Abbastabar, H., Abd-Allah, F., Abdela, J., Abdelalim, A., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)32279-7 · Cited by 13,867
Vos, T., Abajobir, A. A., Abate, K. H., Abbafati, C., Abbas, K. M., Abd-Allah, F., Abdulkader, R. S., Abdulle, A. M., Abebo, T. A., Abera, S. F., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)32154-2 · Cited by 13,220
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
Kim, J., Kundu, M., Viollet, B., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2152 · Cited by 7,227
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., & Shimizu, N. (1998) · Nature · doi:10.1038/33416 · Cited by 5,227
AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602
Cited by
Sorted by citations
Molecular mechanisms of aging and anti-aging strategies
Li, Y., Tian, X., Luo, J., Bao, T., Wang, S., & Wu, X. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01663-1 · Cited by 380
The role of AMPK in macrophage metabolism, function and polarisation
Cui, Y., Chen, J., Zhang, Z., Shi, H., Sun, W., & Yi, Q. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04772-6 · Cited by 213
Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease
Yan, Q., Liu, S., Sun, Y., Chen, C., Yang, S., Lin, M., Long, J., Yao, J., Lin, Y.-T., Yi, F., et al. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04361-7 · Cited by 184
Yue, D., Zhang, Q., Zhang, J., Liu, W., Chen, L., Wang, M., Li, R., Qin, S., Song, X., & Ji, Y. (2022) · Environment International · doi:10.1016/j.envint.2022.107706 · Cited by 147
The role of aldehyde dehydrogenase 2 in cardiovascular disease
Zhang, J., Guo, Y., Zhao, X., Pang, J., Pan, C., Wang, J., Wei, S., Yu, X., Zhang, C., Chen, Y., et al. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00839-5 · Cited by 142
Metadata
- Authors
- Wu, S., & Zou, M.-H.
- Affiliations
- Georgia State University (US)
- Corresponding author
- Wu, Shengnan
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2020-07-15
- Volume
- 21
- Issue
- 14
- Pages
- 4987
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7404275
- OpenAlex
- W3043111807
- Cited by
- 286
- References
- 278
- Citations by year
- 2026: 48 · 2025: 71 · 2024: 50 · 2023: 45 · 2022: 43 · 2021: 27 · 2020: 2
- FWCI
- 2.80
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- American Heart Association (16POST29960011, 19CDA34760110)
- Georgia Research Alliance
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- AMPK, mitochondrial dysfunction, mitochondrial homeostasis, cardiovascular disease, redox sensing, energy homeostasis, statins, metformin, berberine, polyphenols, resveratrol
- MeSH terms
- Adenosine Triphosphate, Animals, Cardiovascular Diseases, Energy Metabolism, Humans, Mitochondria, Reactive Oxygen Species, AMP-Activated Protein Kinases, Mitochondrial Turnover
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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