The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis
Open accessAbstract
Plasma HDL levels have a protective role in atherosclerosis, yet clinical therapies to raise HDL levels have remained elusive. Recent advances in the understanding of lipid metabolism have revealed that miR-33, an intronic microRNA located within the SREBF2 gene, suppresses expression of the cholesterol transporter ABC transporter A1 (ABCA1) and lowers HDL levels. Conversely, mechanisms that inhibit miR-33 increase ABCA1 and circulating HDL levels, suggesting that antagonism of miR-33 may be atheroprotective. As the regression of atherosclerosis is clinically desirable, we assessed the impact of miR-33 inhibition in mice deficient for the LDL receptor (Ldlr-/- mice), with established atherosclerotic plaques. Mice treated with anti-miR33 for 4 weeks showed an increase in circulating HDL levels and enhanced reverse cholesterol transport to the plasma, liver, and feces. Consistent with this, anti-miR33-treated mice showed reductions in plaque size and lipid content, increased markers of plaque stability, and decreased inflammatory gene expression. Notably, in addition to raising ABCA1 levels in the liver, anti-miR33 oligonucleotides directly targeted the plaque macrophages, in which they enhanced ABCA1 expression and cholesterol removal. These studies establish that raising HDL levels by anti-miR33 oligonucleotide treatment promotes reverse cholesterol transport and atherosclerosis regression and suggest that it may be a promising strategy to treat atherosclerotic vascular disease.
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“Furthermore, macrophages within the atherosclerotic lesions of these mice exhibit an anti-inflammatory phenotype characterized by enhanced cholesterol efflux, which leads to a reduction in foam cell formation.”
From Critical Role of microRNA-33a/b in Cardiovascular and Metabolic Disease: Molecular Mechanisms and Therapeutic Perspectives (2026) · cites this paper as [21]
In the citing paper
“Inhibition or genetic ablation of miR-33a has been shown to either promote the regression of atherosclerosis or prevent its formation in mouse models, such as LDL receptor-deficient or apoprotein E (ApoE)-deficient mice, conferring resistance to the disease 21 - 23) .”
From Critical Role of microRNA-33a/b in Cardiovascular and Metabolic Disease: Molecular Mechanisms and Therapeutic Perspectives (2026) · cites this paper as [21]
In the citing paper
“Moreover, the effect of miR-33 deletion in macrophages is not as simple as the shift from the M1 to M2 phenotype reported previously.19”
From MicroRNA‐33 Deficiency Reduces the Progression of Atherosclerotic Plaque in ApoE −/− Mice (2012) · cites this paper as [19]
In the citing paper
“Moreover, antisense inhibition of miR-33 resulted in a regression of the atherosclerotic plaque volume in LDL-receptor-deficient mice.19”
From MicroRNA‐33 Deficiency Reduces the Progression of Atherosclerotic Plaque in ApoE −/− Mice (2012) · cites this paper as [19]
In the citing paper
“In any case, the effect of miR-33 deletion in macrophages is not as simple as a shift from the M1 to the M2 phenotype, as described in a previous report.19”
From MicroRNA‐33 Deficiency Reduces the Progression of Atherosclerotic Plaque in ApoE −/− Mice (2012) · cites this paper as [19]
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Citations
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Background
Metadata
- Authors
- Rayner, K. J., Sheedy, F. J., Esau, C. C., Hussain, F. N., Temel, R. E., Parathath, S., van Gils, J. M., Rayner, A. J., Chang, A. N., Suarez, Y., Fernandez-Hernando, C., Fisher, E. A., & Moore, K. J.
- Affiliations
- New York University (US)
- Regulus Therapeutics (United States) (US)
- Wake Forest University Health Sciences (US)
- Corresponding author
- Moore, Kathryn J.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2011-07-01
- Volume
- 121
- Issue
- 7
- Pages
- 2921-2931
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3223840
- OpenAlex
- W2168964544
- Cited by
- 690
- References
- 0
- Citations by year
- 2026: 14 · 2025: 27 · 2024: 21 · 2023: 35 · 2022: 41 · 2021: 36 · 2020: 38 · 2019: 43 · 2018: 45 · 2017: 48 · 2016: 63 · 2015: 62 · 2014: 82 · 2013: 71 · 2012: 50
- FWCI
- 70.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Funders
- National Institutes of Health (5r00hl088528-05)
- Canadian Institutes of Health Research
- National Institute on Aging (R01AG020255)
- National Heart, Lung, and Blood Institute (R01HL084312, R00-HL088528, K99HL088528, P01HL098055, R01HL108182, R01HL107953)
- 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
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- miR-33, reverse cholesterol transport, HDL cholesterol, atherosclerosis regression, ABCA1, SREBF2, LDL receptor-deficient mice, atherosclerotic plaque, plaque macrophages, cholesterol efflux, plaque stability, inflammation
- MeSH terms
- Animals, Humans, Cholesterol, HDL, Liver, Macrophages, Mice, Inbred C57BL, Random Allocation, Receptors, LDL, Gene Expression, Mice, Knockout, ATP-Binding Cassette Transporters, MicroRNAs, Atherosclerosis, Lipid Metabolism, Mice, ATP Binding Cassette Transporter 1
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