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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
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Lipid profile comparison of tomato extract and atorvastatin supplementation in atherosclerosis rats
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The 10 Most Read Articles Published in Circulation Research in 2013
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“NAs may represent a potential therapeutical intervention for treating dyslipidemia and atherosclerotic vascular disease.(4)”
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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
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 2026-10-17, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-17 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
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