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Control of Cholesterol Metabolism and Plasma High-Density Lipoprotein Levels by microRNA-144
Open accessAbstract
Rationale: Foam cell formation because of excessive accumulation of cholesterol by macrophages is a pathological hallmark of atherosclerosis, the major cause of morbidity and mortality in Western societies. Liver X nuclear receptors (LXRs) regulate the expression of the adenosine triphosphate–binding cassette (ABC) transporters, including adenosine triphosphate–binding cassette transporter A1 (ABCA1) and adenosine triphosphate–binding cassette transporter G1 (ABCG1). ABCA1 and ABCG1 facilitate the efflux of cholesterol from macrophages and regulate high-density lipoprotein (HDL) biogenesis. Increasing evidence supports the role of microRNA (miRNAs) in regulating cholesterol metabolism through ABC transporters. Objective: We aimed to identify novel miRNAs that regulate cholesterol metabolism in macrophages stimulated with LXR agonists. Methods and Results: To map the miRNA expression signature of macrophages stimulated with LXR agonists, we performed an miRNA profiling microarray analysis in primary mouse peritoneal macrophages stimulated with LXR ligands. We report that LXR ligands increase miR-144 expression in macrophages and mouse livers. Overexpression of miR-144 reduces ABCA1 expression and attenuates cholesterol efflux to apolipoproteinA1 in macrophages. Delivery of miR-144 oligonucleotides to mice attenuates ABCA1 expression in the liver, reducing HDL levels. Conversely, silencing of miR-144 in mice increases the expression of ABCA1 and plasma HDL levels. Thus, miR-144 seems to regulate both macrophage cholesterol efflux and HDL biogenesis in the liver. Conclusions: miR-144 regulates cholesterol metabolism via suppressing ABCA1 expression and modulation of miRNAs may represent a potential therapeutical intervention for treating dyslipidemia and atherosclerotic vascular disease.
Overview
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Written from the paper’s full text.
TL;DR
miR-144 is induced by LXR ligands in macrophages and liver and directly represses ABCA1, reducing macrophage cholesterol efflux and hepatic HDL biogenesis. In mice, miR-144 overexpression lowers plasma HDL, whereas miR-144 inhibition raises ABCA1 and HDL, suggesting anti-miR-144 as a possible dyslipidemia/atherosclerosis strategy.
Key findings
- An unbiased miRNA microarray in T090-treated mouse peritoneal macrophages identified 32 differentially regulated miRNAs; miR-144 was predicted to target lipid-metabolism genes and had 7 potential binding sites in the ABCA1 3′UTR.
- miR-144 overexpression reduced ABCA1 mRNA/protein and attenuated cholesterol efflux to ApoA1 in macrophages; anti-miR-144 increased ABCA1 and efflux. In vivo, miR-144 mimic delivery produced a 250-fold increase in liver miR-144, reduced liver ABCA1, and significantly lowered total and HDL cholesterol without changing TG or other lipoprotein distributions.
- miR-144 inhibition reduced miR-144 levels and increased liver ABCA1 protein; after T090, miR-144 was induced 2.3-fold and inhibited 2.1-fold by anti-miR-144, with increased plasma HDL cholesterol.
- miR-33 and miR-144 co-transfection reduced Abca1 3′UTR luciferase activity by 60%, compared with 30–40% suppression by either miRNA alone, suggesting additive regulation of ABCA1.
Methods
- Primary mouse peritoneal macrophages were stimulated with 3 μmol/L T090 for 24 h and profiled by Illumina miRNA microarrays; differential expression used unpaired t-test with p<0.2 and fold change ≥1.5, without multiple-testing correction.
- In vitro studies used miR-144 mimics/inhibitors in mouse peritoneal macrophages, J774, THP-1, HepG2, Huh-7, Hepa, and EAhy926 cells; ABCA1/ABCG1 expression, 3′UTR luciferase reporters, and 3H-cholesterol efflux to ApoA1 were measured.
- In vivo, 8-week-old male C57BL/6 mice were randomized into 4 groups (n=24 total; n=6/group) and injected intravenously twice every three days with control or miR-144 mimic/inhibitor at 7 mg/kg; some mice also received T090 (10 mg/kg) by oral gavage. Plasma lipids and FPLC lipoprotein fractions were analyzed.
Limitations
- The paper states that detailed methods are in the supplemental material due to space limits, and that whether LXR regulates pri-miR-144/451 by direct promoter interaction remains unanswered; further experiments are warranted to understand transcriptional regulation.
- The paper notes that the lack of further cholesterol-efflux reduction with combined miR-33/miR-144 may reflect the very low 5 nM mimic dose and T090-induced endogenous miR-144 in hepatic cells but not in COS-7 cells used for 3′UTR assays.
- Evident from the text: the microarray screen used a relaxed p<0.2 threshold with no multiple-testing correction, in vivo groups were small (n=6), and the study reports lipid/HDL endpoints rather than atherosclerosis outcomes.
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Claims the paper makes
46 Own result · 15 Own interpretation · 6 Own method · 1 No full text of the sources · 1 Not checked yet
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Delivery of miR-144 oligonucleotides to mice attenuates ABCA1 expression in the liver, reducing HDL levels.”
- Also stated in: § INTRODUCTION · plain
“in vivo delivery of miR-144 to mice represses ABCA1 expression in the liver, reducing circulating HDL levels.”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > Abstract > Methods and Results
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.
- Also stated in: § INTRODUCTION · plain
A result the paper reports from its own data — 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 contrast to ABCA1, ABCG1 expression was slightly reduced in miR-144 over-expressing macrophages.”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-144 regulates ABCA1 expression in macrophages and hepatic cells
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.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover ABCG1 was also down-regulated at the mRNA level in macrophages transfected with miR-144 (Figure 3A, right panel).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-144 regulates ABCA1 expression in macrophages and hepatic cells
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Transfection of mouse peritoneal macrophages with miR-144 increased its expression 350-fold (not shown) and significantly inhibited ABCA1 mRNA levels (Figure 3A, left panel).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-144 regulates ABCA1 expression in macrophages and hepatic cells
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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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, hepatic miR-144 levels are regulated by high fat diet in vivo (Online Figure IIIC, right panel).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-144 is up-regulated in LXR-activated macrophages and in the liver of mice fed with high fat diet
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.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We report that LXR ligands increase miR-144 expression in macrophages and mouse livers.”
- Also stated in: § miR-144 is up-regulated in LXR-activated macrophages and in the liver of mice fed with high fat diet · plain
“mouse peritoneal macrophages, human monocytes (THP-1) and human hepatic (Huh-7) cells treated with T090 showed an increased expression of miR-144.”
- Also stated in: § miR-144 is up-regulated in LXR-activated macrophages and in the liver of mice fed with high fat diet · boosted
“Collectively, these data demonstrated that treatment of macrophages and hepatic cells with a LXR agonist resulted in higher expression of miR-144.”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > Abstract > Methods and Results
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.
- Also stated in: § miR-144 is up-regulated in LXR-activated macrophages and in the liver of mice fed with high fat diet · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overexpression of miR-144 reduces ABCA1 expression and attenuates cholesterol efflux to ApoA1 in macrophages.”
- Also stated in: § INTRODUCTION · plain
“miR-144 over-expression inhibits ABCA1 expression in different cell lines including hepatocytes and monocyte/macrophages, thereby attenuating cholesterol efflux to apolipoprotein A1 (ApoA1).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > Abstract > Methods and Results
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.
- Also stated in: § INTRODUCTION · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“after cholesterol loading with acetylated low-density lipoproteins (Ac-LDL) in mouse peritoneal macrophages (Online Figure IIB).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-144 is up-regulated in LXR-activated macrophages and in the liver of mice fed with high fat diet
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, we also found that the miR-144/451 promoter activity was induced in Huh-7 cells treated with T090 (Figure 2E).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-144 is up-regulated in LXR-activated macrophages and in the liver of mice fed with high fat diet
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overexpression of miR-144 reduces ABCA1 expression and attenuates cholesterol efflux to ApoA1 in macrophages.”
- Also stated in: § miR-144 regulates ABCA1 expression in macrophages and hepatic cells · plain
“Transfection of mouse peritoneal macrophages with miR-144 increased its expression 350-fold (not shown) and significantly inhibited ABCA1 mRNA levels (Figure 3A, left panel).”
- Also stated in: § miR-144 regulates ABCA1 expression in macrophages and hepatic cells · boosted
“Transfection of mouse peritoneal macrophages with miR-144 mimics but not a control miRNA (Con-miR) strongly decreased the stimulation of ABCA1 (Figure 3B, left panel).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > Abstract > Methods and Results
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.
- Also stated in: § miR-144 regulates ABCA1 expression in macrophages and hepatic cells · plain
- It may state two separate claims as one. 14
- Probably not a substantial claim. 8
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“miR-144 was widely expressed in mouse tissues and is particularly abundant in the liver, spleen and aorta (Online Figure IIIA).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-144 is up-regulated in LXR-activated macrophages and in the liver of mice fed with high fat diet
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Co-transfection of miR-33 and miR-144 resulted in a 60% decrease in luciferase activity whereas miR-144 or miR-33 alone suppressed the 3’UTR activity 30-40% (Figure 4B).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-33 and miR-144 have an additive effect on ABCA1 protein expression
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.
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In the paper
“miR-33 and miR-144 inhibited cholesterol efflux but the combination of both miRNAs do not further reduced the cholesterol export in this human hepatic cell line (Figure 4C).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-33 and miR-144 have an additive effect on ABCA1 protein expression
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.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As expected plasma TG levels were slightly increased after T090 treatment but no differences were not affected by anti-miR-144 treatment (Figure 7D, right panel).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-144 expression regulates cellular cholesterol efflux and HDL levels in vivo
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.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, antagonism of endogenous miR-144 increased ABCA1 expression (Figure 5B, upper panel) and cellular cholesterol efflux to ApoA1 (Figure 5B, bottom panel).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-144 expression regulates cellular cholesterol efflux and HDL levels in vivo
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The inhibition of ABCA1 expression after 6 days of treatment with miR-144 particles leads to a significant reduction in total cholesterol and HDL cholesterol levels without changes in TG or cholesterol distribution in other lipoproteins (Figure 6C and D).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-144 expression regulates cellular cholesterol efflux and HDL levels in vivo
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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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As expected, miR-144 over-expression inhibited ABCA1 expression (Figure 5A, upper panel) and attenuated cholesterol efflux to ApoA1 (Figure 5A, bottom panel).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-144 expression regulates cellular cholesterol efflux and HDL levels in vivo
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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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The data show that miR-144 inhibition in basal conditions resulted in a significant reduction of miR-144 levels (Figure 7A) and an increase of liver ABCA1 protein expression without changes at the mRNA level (Figure 7B and C upper panel).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-144 expression regulates cellular cholesterol efflux and HDL levels in vivo
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“As seen in Online Figure VIA, inhibition of miR-144 does not alter miR-33 levels and miR-33 inhibition does not change miR-144 expression.”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-33 and miR-144 have an additive effect on ABCA1 protein expression
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Under this condition, miR-144 was induced 2.3-fold and inhibited 2.1-fold after the injection of anti-miR-144 oligonucleotides (Figure 7A).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-144 expression regulates cellular cholesterol efflux and HDL levels in vivo
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Thus, miR-144 appears to regulate both macrophage cholesterol efflux and HDL biogenesis in the liver.”
- Also stated in: § INTRODUCTION · hedged
“Thus, miR-144 appears to regulate both macrophage cholesterol efflux and HDL biogenesis in the liver.”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > Abstract > Methods and Results
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § INTRODUCTION · hedged
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The 1.5-fold-change threshold was chosen on the basis of its use in previously published articles employing these particular types of microarrays.”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > METHODS > miRNA microarray analysis
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Quadruplicates for each condition were used for microarray analysis.”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > METHODS > miRNA microarray analysis
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The expression of both ABCA1 and ABCG1 are up-regulated in states of cholesterol excess by LXR 9.”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites [9] Venkateswaran A Laffitte BA Joseph SB Mak PA Wilpitz DC Edwards PA Tontonoz P Control of cellular cholesterol efflux by the nuclear oxysterol receptor lxr alpha Proc Natl Acad Sci U S A 2000 97 12097 12102 11035776 PMC17300 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Eight-week-old male C57BL/6 mice were randomized into 4 groups (n= 24 mice): non-targeting control mimic (Con-mir, n=6), miR-144-mimic (miR-144, n=6), inhibitor negative control sequence (Con-inh, n=6) and miR-144-inhibitors (Inh-miR-144).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > METHODS > Animals
plainn = 24- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
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
“Altogether, these results establish that miR-144 overexpression or inhibition reduces and increases circulating HDL, respectively.”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-144 expression regulates cellular cholesterol efflux and HDL levels in vivo
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The purity and integrity of both the total RNA sample and the enriched miRNA was verified using the Agilent Bioanalyzer (Agilent Technologies, Santa Clara, CA).”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > METHODS > miRNA microarray analysis
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“We have previously reported that miR-33, an intronic miRNA encoded in the Srebp genes, regulates ABCA1 expression.”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > RESULTS > miR-33 and miR-144 have an additive effect on ABCA1 protein expression
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Verification of miR-144 over-expression and knockdown was determined using qPCR, as described above.”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > METHODS > miR-144 mimic and anti-miR-144 transfection
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
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In the paper
“All experimental control samples were treated with an equal concentration of a non-targeting control mimic sequence (Con-miR) or inhibitor negative control sequence (Con-inh), for use as controls for non-sequence-specific effects in miRNA experiments.”
§ Control of Cholesterol Metabolism and Plasma HDL Levels by miRNA-144 > METHODS > miR-144 mimic and anti-miR-144 transfection
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
The paper relies on this without support.
ABCA1 and ABCG1 facilitate cholesterol efflux from macrophages and regulate HDL biogenesis.
“ABCA1 and ABCG1 facilitate the efflux of cholesterol from macrophages and regulate high-density lipoprotein (HDL) biogenesis.”
“Several ABC transporters, including ABCA1 and ABCG1, facilitate the efflux of cholesterol from macrophages.”
The paper relies on this without support.
In the liver, ABCA1 plays a critical role in HDL biogenesis and its deficiency leads to a dramatic reduction of plasma HDL levels.
“In the liver, ABCA1 also plays a critical role in the biogenesis of HDL and its deficiency leads to a dramatic reduction of plasma HDL levels.”
The paper relies on this without support.
ABCA1 plays a critical role in regulating cellular cholesterol efflux to ApoA1.
“ABCA1 plays a critical role in regulating cellular cholesterol efflux to ApoA1.”
The paper relies on this without support.
ABCA1 plays a key role in regulating HDL biogenesis in the liver.
“In addition to regulating cellular cholesterol efflux, ABCA1 plays a key role in regulating HDL biogenesis in the liver.”
The paper relies on this without support.
Hepatic ABCA1 is critical for the generation of plasma HDL.
“Finally, because hepatic ABCA1 is critical for the generation of plasma HDL, it seems likely that a combination therapy that includes both miR-144 and miR-33 antisense oligonucleotides might result in increased HDL levels, thus improving the prognosis for patients with cardiovascular disease.”
Citations
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“Macrophages cannot limit the uptake of cholesterol and, therefore, depend on cholesterol efflux pathways for preventing their transformation into foam cells.(1,2) Several ABC transporters, including adenosine triphosphate–binding cassette transporter A1 (ABCA1) and adenosine triphosphate– binding cassette transporter…”
BackgroundmiR-122 regulation of lipid metabolism revealed by in vivo antisense targeting
Esau, C., Davis, S., Murray, S. F., Yu, X. X., Pandey, S. K., Pear, M., Watts, L., Booten, S. L., Graham, M., McKay, R., et al. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.005 · Cited by 2,082 · cited 2×
“Interestingly some of the miRNAs induced by T090, including miR-370 and miR-122, were previously identified as important regulators of lipid metabolism.(15,16,18,28) To determine the potential candidates involved in regulating cholesterol metabolism, we analyzed the predicted target genes using a combination of bioinf…”
BackgroundMethodMutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency
Brooks-Wilson, A., Marcil, M., Clee, S. M., Zhang, L.-H., Roomp, K., van Dam, M., Yu, L., Brewer, C., Collins, J. A., Molhuizen, H. O. F., et al. (1999) · Nature Genetics · doi:10.1038/11905 · Cited by 1,687
Cited by
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Bile acid signaling in metabolic disease and drug therapy
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MicroRNA Regulation of Atherosclerosis
Feinberg, M. W., & Moore, K. J. (2016) · Circulation Research · doi:10.1161/circresaha.115.306300 · Cited by 638
Circulating microRNAs as novel biomarkers for platelet activation.
Willeit, P., Zampetaki, A., Dudek, K., Kaudewitz, D., King, A., Kirkby, N. S., Crosby-Nwaobi, R., Prokopi, M., Drozdov, I., Langley, S. R., et al. (2013) · Circulation Research · doi:10.1161/circresaha.111.300539 · Cited by 365
“Conclusions—miR-144 regulates cholesterol metabolism via suppressing ABCA1 expression, and modulation of miRNAs may represent a potential therapeutical intervention for treating dyslipidemia and atherosclerotic vascular disease.(4)”
BackgroundMicroRNA-mediated regulation of glucose and lipid metabolism
Agbu, P., & Carthew, R. W. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00354-w · Cited by 376
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MicroRNA-223 coordinates cholesterol homeostasis
Vickers, K. C., Landstreet, S. R., Levin, M. G., Shoucri, B. M., Toth, C. L., Taylor, R. C., Palmisano, B. T., Tabet, F., Cui, H. L., Rye, K.-A., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215767111 · Cited by 253
MicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels
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ATP-Binding Cassette Transporters, Atherosclerosis, and Inflammation
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MicroRNAs and lipid metabolism
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The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease
Jacobo‐Albavera, L., Domínguez‐Pérez, M., Medina-Leyte, D. J., González-Garrido, A., & Villarreal-Molina, M. T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041593 · Cited by 172
“In addition, two independent research groups stated that miR-144, an intergenic miRNA present in the miR-451 bicistronic cluster, also targets liver ABCA1 and modulates HDL-cholesterol plasma levels [53,54].”
BackgroundNguyen, M.-A., Wyatt, H., Susser, L., Geoffrion, M., Rasheed, A., Duchez, A., Cottee, M. L., Afolayan, E., Farah, E., Kahiel, Z., et al. (2019) · ACS Nano · doi:10.1021/acsnano.8b09679 · Cited by 158
miRNAs in atherosclerotic plaque initiation, progression, and rupture
Andreou, I., Sun, X., Stone, P. H., Edelman, E. R., & Feinberg, M. W. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.02.003 · Cited by 155
“Similarly, miR-27 [63], miR-144 [64, 65], miR-145 [66, 67], miR-223 [68], and miR-758 [69] post-transcriptionally regulate cellular cholesterol efflux to apolipoprotein A-I by suppression of ABCA1 expression.”
The long noncoding RNA CHROME regulates cholesterol homeostasis in primates
Hennessy, E. J., Solingen, C. V., Scacalossi, K. R., Ouimet, M. I., Afonso, M. S., Prins, J., Koelwyn, G. J., Sharma, M., Ramkhelawon, B., Carpenter, S. B., et al. (2018) · Nature Metabolism · doi:10.1038/s42255-018-0004-9 · Cited by 150
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“…↓ ↓ Adlakha et al., 2013; DiMarco and Fernandez, 2015 miR-130b ↓ Wagschal et al., 2015; Feinberg and Moore, 2016 miR-144 ↓ ↓ (Indirect via RXR) de Aguiar Vallim et al., 2013; Kang et al., 2013; Ramírez et al., 2013; Canfrán-Duque et al., 2014; Goedeke et al., 2014; Rayner and Moore, 2014; DiMarco…”
Liver microRNAs: potential mediators and biomarkers for metabolic and cardiovascular disease?
Willeit, P., Skroblin, P., Kiechl, S. J., Fernandez-Hernando, C. F., & Mayr, M. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw146 · Cited by 128
Regulation of High-Density Lipoprotein Metabolism
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Modulation of Hypercholesterolemia‐Induced Oxidative/Nitrative Stress in the Heart
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“miR-144 up Liver ABCA1 down Reverse cholesterol transport [28]”
BackgroundMicroRNA-mediated mechanisms of the cellular stress response in atherosclerosis
Schober, A., Nazari-Jahantigh, M., & Weber, C. (2015) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2015.38 · Cited by 114
microRNAs in lipoprotein metabolism and cardiometabolic disorders
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Self-citationMechanistic Role of MicroRNAs in Coupling Lipid Metabolism and Atherosclerosis
Novák, J., Olejníčková, V., Tkáčová, N., & Santulli, G. (2015) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-22380-3_5 · Cited by 95
MicroRNA 302a Is a Novel Modulator of Cholesterol Homeostasis and Atherosclerosis
Meiler, S. U., Baumer, Y., Toulmin, E., Seng, K., & Boisvert, W. A. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.304878 · Cited by 111
Characterization of microRNAs differentially expressed during bovine follicle development
Sontakke, S. D., Mohammed, B., McNeilly, A. S., & Donadeu, F. X. (2014) · Reproduction · doi:10.1530/rep-14-0140 · Cited by 107
“2013) (Ramirez et al .”
Regulation of ABCA1 Protein Expression and Function in Hepatic and Pancreatic Islet Cells by miR-145
Kang, M. H., Zhang, L., Wijesekara, N., de Haan, W., Butland, S. L., Bhattacharjee, A., & Hayden, M. R. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.302004 · Cited by 104
microRNAs in the onset and development of cardiovascular disease
Vickers, K. C., Rye, K., & Tabet, F. (2013) · Clinical Science · doi:10.1042/cs20130203 · Cited by 102
“Recently, another miRNA, miR-144, has been reported to regulate the expression of ABCA1 in macrophages and hepatocytes [60].”
BackgroundInfluentialThe Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress
Włodarski, A., Strycharz, J., Wróblewski, A. M., Kasznicki, J., Drzewoski, J., & Śliwińska, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186902 · Cited by 99
Noncoding RNAs and Atherosclerosis
Aryal, B. K., Rotllán, N., & Fernandez-Hernando, C. F. (2014) · Current Atherosclerosis Reports · doi:10.1007/s11883-014-0407-3 · Cited by 94
MicroRNA Control of High-Density Lipoprotein Metabolism and Function
Rayner, K. J., & Moore, K. J. (2014) · Circulation Research · doi:10.1161/circresaha.114.300645 · Cited by 91
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“The overexpression of miR-144 reduces ABCA1 expression, while the silencing of miR-144 in mice increases the expression of ABCA1 and plasma HDL levels (Ramirez et al., 2013).”
BackgroundOxidative stress in atherosclerosis: The role of microRNAs in arterial remodeling
Zampetaki, A., Dudek, K., & Mayr, M. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.06.025 · Cited by 79
“MiR-144 Macrophages ABCA1 Cholesterol efflux [81,82]”
Vega‐Badillo, J., Gutiérrez‐Vidal, R., Hernández‐Pérez, H. A., Villamil‐Ramírez, H., León‐Mimila, P., Sánchez‐Muñoz, F., Morán‐Ramos, S., Larrieta‐Carrasco, E., Fernández‐Silva, I., Méndez‐Sánchez, N., et al. (2016) · Liver International · doi:10.1111/liv.13109 · Cited by 75
“TLR2 has only one miR-144 binding site, as compared to ABCA1 having 7 miR-144 binding sites (12).”
BackgroundmiR-223 Exerts Translational Control of Proatherogenic Genes in Macrophages
Nguyen, M.-A., Hoang, H.-D., Rasheed, A., Duchez, A.-C., Wyatt, H., Cottee, M. L., Graber, T. E., Susser, L., Robichaud, S., Berber, İ., et al. (2022) · Circulation Research · doi:10.1161/circresaha.121.319120 · Cited by 74
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miR-183 functions as an oncogene by targeting ABCA1 in colon cancer
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“These include miR-758 (42), miR-26 (43), miR-106b (44), miR-10b (45), miR-144 (46, 47), and miR-101 (48).”
MicroRNA modulation of lipid metabolism and oxidative stress in cardiometabolic diseases
Aranda, J. F., Madrigal‐Matute, J., Rotllán, N., & Fernandez-Hernando, C. F. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.07.014 · Cited by 67
“[34] showed that ABCA1 is posttranscriptionally regulated by miR-144 in vitro and in vivo (Fig.”
Self-citationEpigenetic regulation of cholesterol homeostasis
Meaney, S. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00311 · Cited by 68
“This regulatory mechanism appears to be of functional importance, as silencing of these miRNAs in vivo leads to an increase in plasma HDL (Rayner et al., 2011a; Adlakha et al., 2013; Ramírez et al., 2013).”
BackgroundEpigenetic Reprogramming in Atherosclerosis
Grimaldi, V., Vietri, M. T., Schiano, C., Picascia, A., Pascale, M. R. D., Fiorito, C., Casamassimi, A., & Claudio Napoli, A. (2014) · Current Atherosclerosis Reports · doi:10.1007/s11883-014-0476-3 · Cited by 64
Micro-RNAs and High-Density Lipoprotein Metabolism
Canfrán‐Duque, A., Lin, C., Goedeke, L., Suárez, Y., & Fernandez-Hernando, C. F. (2016) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.116.307028 · Cited by 64
Self-citationMicroRNAs in obesity-associated disorders
Abente, E. J., Subramanian, M., Ramachandran, V., & Najafi-Shoushtari, S. H. (2015) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2015.09.018 · Cited by 63
MicroRNA regulation of macrophages in human pathologies
Wei, Y., & Schober, A. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2254-6 · Cited by 65
“5), indicating that LXR activation induces a negative feedback regulation of ABCA1 through miR-144-3p [234, 257].”
Dietary lipids modulate the expression of miR-107, an miRNA that regulates the circadian system
Daimiel, L., Klett‐Mingo, M., Konstantinidou, V., Micó, V., Aranda, J. F., García, B., Martı́nez-Botas, J., Dávalos, A., Fernandez-Hernando, C. F., & Ordovás, J. M. (2014) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201400616 · Cited by 58
“Several miRNAs have been described that modulate important metabolic processes such as Chol efflux [25–29], hepatic metabolism [30,31], cardiovascular development and function [32,33], function of endothelial cells [34] and insulin signaling [35,36].”
BackgroundSelf-citationCanfrán‐Duque, A., Ramírez, C. M., Goedeke, L., Lin, C., & Fernandez-Hernando, C. F. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu140 · Cited by 59
Self-citationmicroRNAs in lipoprotein and lipid metabolism: from biological function to clinical application
Desgagné, V., Bouchard, L., & Guérin, R. (2016) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2016-0575 · Cited by 57
Macrophage Functions in Atherosclerosis
Zeller, I., & Srivastava, S. (2014) · Circulation Research · doi:10.1161/circresaha.114.305641 · Cited by 57
Relevance of microRNA in metabolic diseases
Price, N. L., Ramírez, C. M., & Fernandez-Hernando, C. F. (2014) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408363.2014.937522 · Cited by 55
Self-citationPosttranscriptional regulation of lipid metabolism by non-coding RNAs and RNA binding proteins
Singh, A. K., Aryal, B. K., Zhang, X., Fan, Y., Price, N. L., Suárez, Y., & Fernandez-Hernando, C. F. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.11.026 · Cited by 55
“Inhibition of miR-148a and miR-144 increases hepatic ABCA1 expression and plasma HDL-C levels in mice [32, 34, 70, 71].”
BackgroundSelf-citationNon-coding RNAs in lipid metabolism
Zhang, X., Price, N. L., & Fernandez-Hernando, C. F. (2018) · Vascular Pharmacology · doi:10.1016/j.vph.2018.06.011 · Cited by 54
“In addition to the well-known role of miR-33 in controlling ABCA1 expression and cholesterol efflux, other miRNAs including miR-144, miR-148a, miR-758, miR-26, miR-106b, miR-27, miR-145, miR-20a/b and miR-10b, have been shown to regulate ABCA1 expression at the post-transcriptional level in a variety of different cell…”
Novák, J., Vašků, J. B., Kára, T., & Novák, M. (2014) · Mediators of Inflammation · doi:10.1155/2014/275867 · Cited by 53
“mice [23], indicating that both LXR and FXR controlmiR-144 expression and thus ABCA1 function.”
BackgroundResultInfluentialmicroRNAs: A connection between cholesterol metabolism and neurodegeneration
Goedeke, L., & Fernandez-Hernando, C. F. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.05.034 · Cited by 49
“…have been shown to regulate the expression of ABCA1, a cholesterol transporter that plays a key role in HDL biogenesis and cholesterol efflux (de Aguiar Vallim et al, 2013; Kang et al, 2013; Kim et al, 2012; Marquart et al, 2010; Ramirez et al, 2011; Ramirez et al, 2013; Rayner et al, 2010).”
BackgroundSelf-citationYang, Z., Chen, L., Hong, M. H., Chen, Y., Yang, X., Tang, S.-M., Yuan, Q.-F., & Chen, W. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.6239 · Cited by 49
MicroRNAs in dysfunctional adipose tissue: cardiovascular implications
Icli, B., & Feinberg, M. W. (2017) · Cardiovascular Research · doi:10.1093/cvr/cvx098 · Cited by 50
Pathobiology of biliary epithelia
Cheung, A., Pisarello, M. J. L., & LaRusso, N. F. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.06.024 · Cited by 47
RNA binding protein HuR regulates the expression of ABCA1
Ramírez, C. M., Lin, C., Abdelmohsen, K., Goedeke, L., Yoon, J., Madrigal‐Matute, J., Martín-Ventura, J. L., Vo, D. T., Uren, P. J., Penalva, L. O. F., et al. (2014) · Journal of Lipid Research · doi:10.1194/jlr.m044925 · Cited by 44
Self-citationMicroRNAs and Circular RNAs in Lipoprotein Metabolism
Fernández‐Tussy, P., Ruz‐Maldonado, I., & Fernandez-Hernando, C. F. (2021) · Current Atherosclerosis Reports · doi:10.1007/s11883-021-00934-3 · Cited by 44
The Regulation of Reverse Cholesterol Transport and Cellular Cholesterol Homeostasis by MicroRNAs
DiMarco, D. M., & Fernández, M. L. (2015) · Biology · doi:10.3390/biology4030494 · Cited by 44
Lü, L., He, M., Zhou, L., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.584953 · Cited by 44
Shao, D., Lian, Z., Di, Y., Zhang, L., Rajoka, M. S. R., Zhang, Y., Kong, J., Jiang, C., & Shi, J. (2018) · npj Science of Food · doi:10.1038/s41538-018-0022-8 · Cited by 49
Banno, A., Wang, J., Okada, K., Mori, R., Mijiti, M., & Nagaoka, S. (2019) · Scientific Reports · doi:10.1038/s41598-019-56031-8 · Cited by 46
miRNA and cholesterol homeostasis
Jeon, T.-I., & Osborne, T. F. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.01.005 · Cited by 43
“Conversely, miR-144 is up-regulated by LXR under similar conditions and targets ABCA1, suggesting the presence of negative-feedback regulation in the cholesterol efflux process [55].”
BackgroundMicroRNA regulation of cholesterol metabolism
Citrin, K. M., Fernandez-Hernando, C. F., & Suárez, Y. (2021) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14566 · Cited by 45
Self-citationmiR-206 controls LXRα expression and promotes LXR-mediated cholesterol efflux in macrophages
Vinod, M., Chennamsetty, I., Colin, S., Belloy, L., De Paoli, F., Schaider, H., Graier, W. F., Frank, S., Kratky, D., Staels, B., et al. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.02.006 · Cited by 44
“Recently two independent groups published an LXRα and farnesoid X receptor (FXR) induced expression ofmiR-144 that targeted ABCA1 mRNA and reduced ABCA1mediated cholesterol homeostasis in the liver [24,25].”
BackgroundRegulation of cholesterol biosynthesis and lipid metabolism: A microRNA management perspective
Bhattarai, A., Likos, E., Weyman, C. M., & Shukla, G. C. (2021) · Steroids · doi:10.1016/j.steroids.2021.108878 · Cited by 44
MiR-486 regulates cholesterol efflux by targeting HAT1
Liu, D., Zhang, M., Xie, W., Lan, G., Cheng, H., Gong, D., Huang, C., Lv, Y.-C., Yao, F., Tan, Y. L., et al. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.11.128 · Cited by 41
MicroRNA-144 Silencing Protects Against Atherosclerosis in Male, but Not Female Mice
Cheng, J., Cheng, A., Clifford, B. L., Wu, X., Hedin, U., Mäegdefessel, L., Pamir, N., Sallam, T., Tarling, E. J., & Vallim, T. Q. D. A. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.313633 · Cited by 43
Christian, P., & Su, Q. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00194.2014 · Cited by 42
“(74) have also revealed that there is a regulatory circuit between LXR, ABCA1 and miR-144.”
BackgroundMicroRNA 27a Is a Key Modulator of Cholesterol Biosynthesis
Khan, A. A., Agarwal, H., Reddy, S. S., Arige, V., Natarajan, B., Gupta, V., Ananthamohan, K., Barthwal, M. K., & Mahapatra, N. R. (2020) · Molecular and Cellular Biology · doi:10.1128/mcb.00470-19 · Cited by 41
“Notably, miR-29a, miR-185, miR-150, miR-548p, miR-21, miR-195 and miR-342 have so far been reported to interact with the Hmgcr transcript [25-31].”
BackgroundDiagnostic and theranostic microRNAs in the pathogenesis of atherosclerosis
Shoeibi, S. (2019) · Acta Physiologica · doi:10.1111/apha.13353 · Cited by 40
miR-144/451 in hematopoiesis and beyond
Wang, T., Wu, F., & Yu, D. (2019) · ExRNA · doi:10.1186/s41544-019-0035-8 · Cited by 41
The myriad essential roles of microRNAs in cardiovascular homeostasis and disease
Neppl, R. L., & Wang, D. (2014) · Genes & Diseases · doi:10.1016/j.gendis.2014.06.003 · Cited by 36
Fu, X., Huang, X., Li, P., Chen, W., & Xia, M. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.03.010 · Cited by 36
MicroRNAs in Macrophages: Regulators of Activation and Function
Sprenkle, N. T., Serezani, C. H., & Pua, H. H. (2023) · The Journal of Immunology · doi:10.4049/jimmunol.2200467 · Cited by 39
Zambrano, T., Hirata, R. D. C., Hirata, M. H., Cerda, Á., & Salazar, L. A. (2018) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2018.02.007 · Cited by 36
“…an essential role in the reverse cholesterol transport (RCT) pathway, and has been experimentally validated as a target of miRNA33 (Horie et al., 2010; Marquart et al., 2010; Najafi-Shoushtari et al., 2010; Rayner et al., 2010), miR-758 (Ramirez et al., 2011) and miRNA144 (Ramirez et al., 2013).”
BackgroundmicroRNA regulation of lipoprotein metabolism
Goedeke, L., Aranda, J. F., & Fernandez-Hernando, C. F. (2014) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000094 · Cited by 35
Self-citationMicroRNA-221 may be involved in lipid metabolism in mammary epithelial cells
Chu, M., Zhao, Y. M., Yu, S., Hao, Y., Zhang, P., Feng, Y., Zhang, H., Ma, D., Liu, J., Cheng, M. Y., et al. (2018) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2018.02.014 · Cited by 34
Genomic Variants and Multilevel Regulation of ABCA1, ABCG1, and SCARB1 Expression in Atherogenesis
Rozhkova, A. V., Dmitrieva, V. G., Nosova, E. V., Dergunov, A. D., Limborska, S. A., & Dergunova, L. V. (2021) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd8120170 · Cited by 39
“MiR-144 directly interacted with the 3′-UTR of ABCA1 and decreased its expression and cholesterol efflux to apoA-I [175,176,178].”
BackgroundFu, H., Tang, Y., Ouyang, X.-P., Tang, S., Su, H., Li, X., Huang, L.-P., He, M., Lv, Y.-C., He, P., et al. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.08.120 · Cited by 34
ATP-binding cassette transporter A1
Eck, M. V. (2014) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000088 · Cited by 35
Hsa-miR-140-5p down-regulates LDL receptor and attenuates LDL-C uptake in human hepatocytes
Xu, Y., Gao, J., Gong, Y., Chen, M., Chen, J., Zhao, W., & Tan, S. (2020) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2020.02.004 · Cited by 34
Görür, A., Çelik, A., Yıldırım, D. D., Gündeş, A., & Tamer, L. (2019) · Molecular Biology Reports · doi:10.1007/s11033-018-4547-3 · Cited by 33
Ramírez, C. M., Torrecilla-Parra, M., Pardo-Marqués, V., de-Frutos, M. F., Pérez-García, A., Tabraue, C., de la Rosa, J. V., Martín-Rodriguez, P., Díaz-Sarmiento, M., Nuñez, U., et al. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.635923 · Cited by 34
“5 mCi/ml [(3)H]-cholesterol for 24 h with or without T0901317 (2 uM) for 12 h (35).”
Self-citationLDL Receptor Pathway Regulation by miR-224 and miR-520d
Salerno, A. G., van Solingen, C., Scotti, E., Wanschel, A. C. B. A., Afonso, M. S., Oldebeken, S. R., Spiro, W., Tontonoz, P., Rayner, K. J., & Moore, K. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00081 · Cited by 33
“, miR-33 (15–17, 33), miR-144 (21, 23), and miR-223 (26)], nuclear SREBP accumulation and lipid synthesis [e.”
Self-citationChen, G., Wu, K., Zhao, T., Ling, S.-C., Liu, W., & Luo, Z. (2019) · Journal of Nutrition · doi:10.1093/jn/nxz282 · Cited by 31
Reimunde, P., Pensado‐López, A., Crende, M. C., Iglesias, V. L., Sanchez, L. E., Torrecilla-Parra, M., Ramírez, C. M., Anfray, C., & Torres, F. (2021) · Cancers · doi:10.3390/cancers13051087 · Cited by 31
Self-citationProto, M., Fiore, D., Piscopo, C., Pagano, C., Galgani, M., Bruzzaniti, S., Laezza, C., Gazzerro, P., & Bifulco, M. (2021) · Progress in Lipid Research · doi:10.1016/j.plipres.2021.101099 · Cited by 30
HDL maturation and remodelling
Ong, K. L., Cochran, B. J., Manandhar, B., Thomas, S. R., & Rye, K. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2022.159119 · Cited by 35
MicroRNA-126 participates in lipid metabolism in mammary epithelial cells
Chu, M., Zhao, Y. M., Feng, Y., Zhang, H., Liu, J., Cheng, M. Y., Li, L., Shen, W., Cao, H., Li, Q., et al. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.05.039 · Cited by 32
Non-Coding RNAs and Lipid Metabolism
Smolle, E., & Haybaeck, J. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms150813494 · Cited by 32
“It was demonstrated that over-expression of miR-144 reduces, and inhibition of miR-144 increases, circulating HDL levels in mice [65].”
BackgroundThe Nuclear Receptor FXR Uncouples the Actions of miR-33 From SREBP-2
Tarling, E. J., Ahn, H., & Vallim, T. Q. D. A. (2015) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.304179 · Cited by 32
“Previous cell-based studies demonstrated that both miR-33 and miR144 could act synergistically to target ABCA1.(20)”
BackgroundInfluentialRegulation of HDL Genes: Transcriptional, Posttranscriptional, and Posttranslational
Kardassis, D., Gafencu, A. V., Zannis, V. I., & Dávalos, A. (2014) · Handbook of experimental pharmacology · doi:10.1007/978-3-319-09665-0_3 · Cited by 30
“2012), the human 30 UTR of ABCA1 has several (up to seven) predicted binding sites for miR-144 (Ramirez et al. 2013).”
BackgroundSelf-citationThe diverse roles of macrophages in metabolic inflammation and its resolution
Ray, A. G., Odum, O., Wiseman, D., & Weinstock, A. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1147434 · Cited by 31
“These results suggest a sexspecific regulation of atherosclerosis development by miR-144 (de Aguiar Vallim et al., 2013; Ramirez et al., 2013; Hu et al., 2014; Cheng et al., 2020).”
BackgroundMicroRNAs and Lipoprotein Metabolism
Horie, T., Baba, O., Kuwabara, Y., Yokode, M., Kita, T., Kimura, T., & Ono, K. (2014) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.20859 · Cited by 29
Tang, X.-E., Li, H., Chen, L., Xia, X.-D., Zhao, Z.-W., Zheng, X., Zhao, G.-J., & Tang, C. (2018) · Cytokine · doi:10.1016/j.cyto.2018.04.028 · Cited by 29
Singh, D., Rai, V., & Agrawal, D. K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213731 · Cited by 29
Living long and ageing well: is epigenomics the missing link between nature and nurture?
The ACUME2 Project, Rea, I. M., Dellett, M., & Mills, K. (2015) · Biogerontology · doi:10.1007/s10522-015-9589-5 · Cited by 29
“MicroRNAs are considered important epigenetic regulators and have been described in many processes related to cardiovascular disease (Ramı́rez et al. 2013) and chronic diseases (Bladé et al.”
Background
Metadata
- Authors
- Ramírez, C. M., Rotllan, N., Vlassov, A. V., Dávalos, A., Li, M., Goedeke, L., Aranda, J. F., Cirera-Salinas, D., Araldi, E., Salerno, A., Wanschel, A., Zavadil, J., Castrillo, A., Kim, J., Suárez, Y., & Fernández-Hernando, C.
- Affiliations
- Universidad de Las Palmas de Gran Canaria (ES)
- From the Leon H. Charney Division of Cardiology, Departments of Medicine and Cell Biology and the Marc and Ruti Bell Vascular Biology and Disease Program (C.M.R., N.R., A.D., L.G., J.F.A., D.C.-S., E.A., A.S., A.W., Y.S., C.F.-H.), Department of Pathology, New York University Center for Health Informatics and Bioinformatics (J.Z.), New York University School of Medicine, New York, New York; Life Technologies, Austin, Texas (A.V.V., M.L.); Instituto de Investigaciones Biomédicas “Alberto Sols,”...
- ORCID
- Venue
- Circulation Research
- Published
- 2013-06-07
- Volume
- 112
- Issue
- 12
- Pages
- 1592-1601
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC3929583
- OpenAlex
- W2120525672
- Semantic Scholar
- 7805b86aa3521ae15aacb68031f440532d0f4b06
- Cited by
- 217
- References
- 37
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 4 · 2023: 9 · 2022: 15 · 2021: 13 · 2020: 12 · 2019: 20 · 2018: 14 · 2017: 15 · 2016: 25 · 2015: 25 · 2014: 41 · 2013: 9
- FWCI
- 29.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- American Heart Association
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- National Institutes of Health (5p30ns069329-02)
- National Institute on Aging (P30 AG0 28383)
- National Heart, Lung, and Blood Institute (R01HL105945, R01 HL106063, R01HL107953)
- National Institute of Neurological Disorders and Stroke (P30-NS069329)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- microRNA-144, cholesterol metabolism, high-density lipoprotein, ABCA1, ABCG1, liver X receptor, macrophage cholesterol efflux, foam cell formation, atherosclerosis, HDL biogenesis, dyslipidemia, miRNA expression profiling, apolipoprotein A-I
- MeSH terms
- Liver X Receptors, Benzenesulfonamides, Animals, Anticholesteremic Agents, Chlorocebus aethiops, Fluorocarbons, Homeostasis, Humans, Hydrocarbons, Fluorinated, Cholesterol, HDL, Macrophages, Male, Mice, Inbred C57BL, Oligonucleotides, Sulfonamides, Apolipoprotein A-I, Mice, Knockout, ATP-Binding Cassette Transporters, COS Cells, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Hepatocytes, MicroRNAs, Mice, Hep G2 Cells, Orphan Nuclear Receptors, Diet, High-Fat, ATP Binding Cassette Transporter 1
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