The cardioprotective effects of carvedilol on ischemia and reperfusion injury by AMPK signaling pathway
Open accessAbstract
Carvedilol, a third generation beta blocker, is in clinical use for heart failure patients. However, besides adrenergic receptor blockade, the pharmacological effects of carvedilol on cardiomyocytes remain unknown. AMP-activated protein kinase (AMPK) is an emerging target recognized for heart failure treatment. The mechanical properties and intracellular Ca2+ properties were measured in isolated cardiomyocyte contractile functions in response to ischemic stress. Treatment of cardiomyocytes with carvedilol augmented phosphorylation of AMPK and downstream acetyl CoA carboxylase (ACC), and ameliorated hypoxia-induced impairment in maximal velocity of shortening (+dL/dt) and relengthening (-dL/dt), and the impaired peak height and peak shortening (PS) amplitude caused by hypoxia. Carvedilol treatment improved calcium homeostasis with rescuing the peak Ca2+ signal, the maximum rate of Ca2+ change during contraction (+dF/dt) and the maximum rate of Ca2+ change during relaxation (-dF/dt) under hypoxia conditions. In mouse hearts perfused ex vivo with carvedilol, the function of post-ischemia left ventricle was improved and an augmentation in myocardial glucose uptake and glucose oxidation, and inhibition of fatty acid oxidation during ischemia and reperfusion. The protective effect of carvedilol was further supported in an in vivo regional ischemia model by ligation of left anterior descending coronary artery (LAD), mice treated with carvedilol followed by LAD occlusion and reperfusion showed significant size reduction in infarcted myocardium and improved cardiac functions. Therefore, Carvedilol as a clinical drug can modulate cardiac AMPK signaling pathway to reduce ischemic insults by ischemia and reperfusion.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Treatment of cardiomyocytes with carvedilol augmented phosphorylation of AMPK and its downstream substrate ACC, and ameliorated hypoxia-induced impairment.
“Treatment of cardiomyocytes with carvedilol augmented phosphorylation of AMPK and its downstream substrate ACC, and ameliorated hypoxia-induced impairment [182].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [182]
Carvedilol treatment improved calcium homeostasis with rescuing the peak Ca2+ signal, the maximum rate of Ca2+ change during contraction and relaxation under hypoxia conditions.
“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].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [182]
Carvedilol modulates cardiac AMPK signaling to reduce ischemic insults by I/R.
“Carvedilol modulates cardiac AMPK signaling to reduce ischemic insults by I/R [182].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [182]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance
Garcia, D., & Shaw, R. J. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.05.032 · Cited by 1,997 · see citing works
Heusch, G., & Gersh, B. J. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw224 · Cited by 679 · see citing works
Stanley, W. C. (1997) · Cardiovascular Research · doi:10.1016/s0008-6363(96)00245-3 · Cited by 606 · see citing works
Opposing Effects of β1- and β2-Adrenergic Receptors on Cardiac Myocyte Apoptosis
Communal, C., Singh, K., Sawyer, D. B., & Colucci, W. S. (1999) · Circulation · doi:10.1161/01.cir.100.22.2210 · Cited by 562 · see citing works
Wallhaus, T. R., Taylor, M., DeGrado, T. R., Russell, D. C., Stanko, P., Nickles, R. J., & Stone, C. K. (2001) · Circulation · doi:10.1161/01.cir.103.20.2441 · Cited by 253 · see citing works
Kudo, N., Gillespie, J. G., Kung, L., Witters, L. A., Schulz, R., Clanachan, A. S., & Lopaschuk, G. D. (1996) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(96)00013-6 · Cited by 246 · see citing works
Gerber, B. L., Vanoverschelde, J., Bol, A., et al. (1996) · Circulation · doi:10.1161/01.cir.94.4.651 · Cited by 207 · see citing works
Sestrin2 promotes LKB1‐mediated AMPK activation in the ischemic heart
Morrison, A., Chen, L., Wang, J., Zhang, M., Yang, H. M., Ma, Y., Budanov, A. V., Lee, J. H., Karin, M., & Li, J. (2014) · The FASEB Journal · doi:10.1096/fj.14-258814 · Cited by 167 · see citing works
Self-citationSantos‐Gallego, C. G., Vahl, T. P., Goliasch, G., Picatoste, B., Arias, T., Ishikawa, K., Njerve, I. U., Sanz, J., Narula, J., Sengupta, P. P., et al. (2016) · Circulation · doi:10.1161/circulationaha.115.012427 · Cited by 165 · see citing works
Ma, H., Wang, J., Thomas, D. P., Tong, C., Leng, L., Wang, W., Merk, M., Zierow, S., Bernhagen, J., Ren, J., et al. (2010) · Circulation · doi:10.1161/circulationaha.110.953208 · Cited by 164 · see citing works
Self-citationBroderick, T. L., Quinney, H. A., Barker, C. C., & Lopaschuk, G. D. (1993) · Circulation · doi:10.1161/01.cir.87.3.972 · Cited by 128 · see citing works
Quan, N., Sun, W., Wang, L., Xu, C., Bogan, J. S., Zhou, X., Cates, C. A., Liu, Q., Zheng, Y., & Li, J. (2017) · The FASEB Journal · doi:10.1096/fj.201700063r · Cited by 124 · see citing works
Self-citationwang, L., Quan, N., Sun, W., Chen, X., Cates, C. A., Rousselle, T. V., Zhou, X., Zhao, X., & Li, J. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy033 · Cited by 122 · see citing works
Self-citationCarvedilol, a novel vasodilating beta-blocker with the potential for cardiovascular organ protection
FEUERSTEIN, G. Z., & Ruffolo, R. R., Jr. (1996) · European Heart Journal · doi:10.1093/eurheartj/17.suppl_b.24 · Cited by 106 · see citing works
Combination treatment with trimetazidine and diltiazem in stable angina pectoris
Manchanda, S. C., & Krishnaswami, S. (1997) · Heart · doi:10.1136/hrt.78.4.353 · Cited by 105 · see citing works
Malonyl CoA Control of Fatty Acid Oxidation in the Ischemic Heart
Dyck, J. R. B., & Lopaschuk, G. D. (2002) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2002.2060 · Cited by 99 · see citing works
Myocardial Energy Substrate Metabolism in Heart Failure : from Pathways to Therapeutic Targets
Fukushima, A., Milner, K., Gupta, A. K., & Lopaschuk, G. D. (2015) · Current Pharmaceutical Design · doi:10.2174/1381612821666150710150445 · Cited by 96 · see citing works
Regulation of carbohydrate metabolism in ischemia and reperfusion
Lopaschuk, G. D. (2000) · American Heart Journal · doi:10.1067/mhj.2000.103919 · Cited by 95 · see citing works
McNulty, P. H., Jagasia, D. H., Cline, G. W., et al. (2000) · Circulation · doi:10.1161/01.cir.101.8.917 · Cited by 65 · see citing works
Ma, Y., Wang, J., Gao, J., Yang, H. M., Wang, Y., Manithody, C., Li, J., & Rezaie, A. R. (2014) · Thrombosis and Haemostasis · doi:10.1160/th14-04-0360 · Cited by 60 · see citing works
Self-citationYang, H. M., Sun, W., Quan, N., et al. (2016) · Biochemical Pharmacology · doi:10.1016/j.bcp.2016.03.019 · Cited by 51 · see citing works
Asanuma, H., Minamino, T., Sanada, S., Takashima, S., Ogita, H., Ogai, A., Asakura, M., Liao, Y., Asano, Y., Shintani, Y., et al. (2004) · Circulation · doi:10.1161/01.cir.0000130917.12959.04 · Cited by 48 · see citing works
Sun, W., Quan, N., Wang, L., Yang, H. M., Chu, D., Liu, Q., Zhao, X., Leng, J., & Li, J. (2016) · Toxicological Sciences · doi:10.1093/toxsci/kfw035 · Cited by 46 · see citing works
Self-citationNikolaidis, L. A., Poornima, I. G., Parikh, P., Magovern, M., Shen, Y., & Shannon, R. P. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.11.082 · Cited by 45 · see citing works
L-Carnitine Attenuates Cardiac Dysfunction by Ischemic Insults Through Akt Signaling Pathway
Xue, M., Chen, X., Guo, Z., Liu, X., Bi, Y., Yin, J., Hu, H., Zhu, P., Zhuang, J., Cates, C. A., et al. (2017) · Toxicological Sciences · doi:10.1093/toxsci/kfx193 · Cited by 23 · see citing works
Self-citationChen, S., Wang, Z., Xu, B., Mi, X., Sun, W., Quan, N., Wang, L., Chen, X., Liu, Q., Zheng, Y., et al. (2015) · Toxicological Sciences · doi:10.1093/toxsci/kfv202 · Cited by 21 · see citing works
Self-citationChen, S., Li, J., Liu, H., et al. (2013) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-013-2391-2 · Cited by 20 · see citing works
Self-citationBøttcher, M., Refsgaard, J., Gøtzsche, O., et al. (2002) · The American Journal of Cardiology · doi:10.1016/s0002-9149(02)02351-2 · Cited by 16 · see citing works
Elnakish, M. T., Hassona, M. D. H., Alhaj, M. A., Moldovan, L., Janssen, P. M. L., Khan, M., & Hassanain, H. H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042500 · Cited by 16 · see citing works
Carvedilol suppresses fatty acid oxidation and stimulates glycolysis in C2C12 cells
Onay-Beşi̇kçi̇, A., Süzmeçelik, E., & Ozcelikay, A. T. (2012) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y2012-015 · Cited by 15 · see citing works
Sun, W., Quan, N., Wang, L., et al. (2016) · Toxicological Sciences · doi:10.1093/toxsci/kfw154 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
AMPK, Mitochondrial Function, and Cardiovascular Disease
Wu, S., & Zou, M.-H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144987 · Cited by 286 · see citing works
Activation of AMPK under Hypoxia: Many Roads Leading to Rome
Dengler, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21072428 · Cited by 133 · see citing works
- Authors
- Hu, H., Li, X., Ren, D., Tan, Y., Chen, J., Yang, L., Chen, R., Li, J., & Zhu, P.
- Affiliations
- University of Mississippi Medical Center (US)
- University of Louisville (US)
- Guangdong Academy of Medical Sciences (CN)
- Corresponding author
- Zhu, Ping
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2019-09
- Volume
- 117
- Pages
- 109106
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W2950834644
- Cited by
- 43
- References
- 31
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 5 · 2021: 9 · 2020: 8 · 2019: 1
- FWCI
- 4.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81570279, 81720102004)
- Natural Science Foundation of Guangdong Province (2017A030312007)
- National Basic Research Program of China (2017YFA0105602, 2018YFA0108700)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- carvedilol, cardioprotection, myocardial ischemia-reperfusion injury, AMPK signaling, beta-blockers, cardiomyocyte contractility, intracellular calcium homeostasis, acetyl-CoA carboxylase, myocardial glucose uptake, fatty acid oxidation, myocardial infarct size, heart failure
- MeSH terms
- Carvedilol, Animals, Cardiotonic Agents, Heart Function Tests, Mice, Inbred C57BL, Myocardial Contraction, Myocardium, Phosphorylation, Signal Transduction, Myocardial Reperfusion Injury, Cell Hypoxia, Calcium Signaling, Myocytes, Cardiac, AMP-Activated Protein Kinases
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.
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 ›
Are you an author, or do you see a problem with this page? Request a review
