Therapeutic Silencing of MicroRNA-33 Inhibits the Progression of Atherosclerosis in Ldlr −/− Mice—Brief Report
Open accessAbstract
Objective—: To study the efficacy of anti–miRNA-33 therapy on the progression of atherosclerosis. Approach and Results—: Ldlr −/− mice were injected subcutaneously with PBS, control, or anti–miR-33 oligonucleotides weekly and fed a Western diet for 12 weeks. At the end of treatment, the expression of miR-33 target genes was increased in the liver and aorta, demonstrating effective inhibition of miR-33 function. Interestingly, plasma high-density lipoprotein (HDL)-cholesterol was significantly increased in anti–miR-33-treated mice but only when they were fed a chow diet. However, HDL isolated from anti–miR-33-treated mice showed an increase cholesterol efflux capacity compared with HDL isolated from nontargeting oligonucleotide-treated mice. Analysis of atherosclerosis revealed a significant reduction of plaque size and macrophage content in mice receiving anti–miR-33. In contrast, no differences in collagen content and necrotic areas were observed among the 3 groups. Conclusions—: Long-term anti–miR-33 therapy significantly reduces the progression of atherosclerosis and improves HDL functionality. The antiatherogenic effect is independent of plasma HDL-cholesterol levels.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Inhibition or genetic ablation of miR-33a promotes regression of atherosclerosis or prevents its formation in mouse models such as LDL receptor-deficient or ApoE-deficient mice, conferring resistance to the disease.
“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 [23]
The Results report smaller atherosclerotic lesions after anti-miR-33 treatment in Ldlr−/− mice. The Discussion also reports plaque regression in a prior Ldlr−/− study and decreased atherosclerosis in miR-33−/− Apoe−/− mice. These passages support reduced disease and regression, but not the stronger claim that atherosclerosis formation was prevented or that the mice were resistant to the disease. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMacrophages within atherosclerotic lesions of these mice exhibit an anti-inflammatory phenotype characterized by enhanced cholesterol efflux, leading to a reduction in foam cell formation.
“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 [23]
The Results (page not provided) report that HDL from anti-miR-33-treated mice increased macrophage cholesterol efflux and that treated plaques had fewer macrophages. The authors suggest this may mediate an anti-inflammatory effect in the artery wall, but they do not establish an anti-inflammatory phenotype in lesion macrophages or show that efflux reduced foam cell formation. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAntagonism of miR-33 in mouse models of atherosclerosis can reduce plaque burden by either impeding the progression or promoting the regression of atherosclerotic plaques.
“Numerous reports have demonstrated that antagonism of miR-33 in mouse models of atherosclerosis can reduce plaque burden by either impeding the progression or promoting the regression of atherosclerotic plaques (Rayner et al., 2011b; Rotllan et al., 2013).”
From Genetic dissection of the impact of miR-33a and miR-33b during the progression of atherosclerosis (2017) · cites this paper as Rotllan et al., 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 10 · Cited by 174
Research works printed but not linked: 6
- [2]Horie T Ono K Horiguchi M Nishi H Nakamura T Nagao K Kinoshita M Kuwabara Y Marusawa H Iwanaga Y Hasegawa K Yokode M Kimura T Kita T Microrna-33 encoded by an intron of sterol regulatory element-binding protein 2 (srebp2) regulates hdl in vivo Proc Natl Acad Sci U S A 2010 107 17321 17326 20855588 PMC2951399
- [3]Marquart TJ Allen RM Ory DS Baldan A Mir-33 links srebp-2 induction to repression of sterol transporters Proc Natl Acad Sci U S A 2010 107 12228 12232 20566875 PMC2901433
- [5]Rayner KJ Suarez Y Davalos A Parathath S Fitzgerald ML Tamehiro N Fisher EA Moore KJ Fernandez-Hernando C Mir-33 contributes to the regulation of cholesterol homeostasis Science 2010 328 1570 1573 20466885 PMC3114628
- [7]Khera AV Cuchel M de la Llera-Moya M Rodrigues A Burke MF Jafri K French BC Phillips JA Mucksavage ML Wilensky RL Mohler ER Rothblat GH Rader DJ Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis The New England journal of medicine 2011 364 127 135 21226578 PMC3030449
- [8]Horie T Baba O Kuwabara Y Microrna-33 deficiency reduces the progression of atherosclerotic plaque in apoe−/− mice Journal of the American Heart Association 2012 1 e003376 23316322 PMC3540673
- [9]Terasaka N Yu S Yvan-Charvet L Wang N Mzhavia N Langlois R Pagler T Li R Welch CL Goldberg IJ Tall AR Abcg1 and hdl protect against endothelial dysfunction in mice fed a high-cholesterol diet J Clin Invest 2008 118 3701 3713 18924609 PMC2567835
- Authors
- Rotllan, N., Ramírez, C. M., Aryal, B., Esau, C. C., & Fernández-Hernando, C.
- Affiliations
- From the Department of Medicine, Leon H. Charney Division of Cardiology and Cell Biology and the Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, New York, NY (N.R., C.M.R., B.A., C.F.-H.); and Regulus Therapeutics, San Diego, CA (C.C.E.).
- New York University (US)
- Regulus Therapeutics (United States) (US)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2013-08
- Volume
- 33
- Issue
- 8
- Pages
- 1973-1977
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC4157595
- OpenAlex
- W2038315143
- Cited by
- 174
- References
- 10
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 5 · 2023: 10 · 2022: 9 · 2021: 14 · 2020: 9 · 2019: 14 · 2018: 14 · 2017: 10 · 2016: 20 · 2015: 19 · 2014: 28 · 2013: 9
- FWCI
- 24.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL106063, R01HL107953)
- Topics
- Health Sciences › Medicine › Surgery › 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
- microRNA-33, atherosclerosis, Ldlr knockout mice, HDL cholesterol, cholesterol efflux capacity, HDL function, atherosclerotic plaque, macrophages, Western diet, microRNA inhibition
- MeSH terms
- Animals, Animal Feed, Injections, Subcutaneous, Cholesterol, HDL, Oligonucleotides, Receptors, LDL, Genetic Therapy, Mice, Knockout, Disease Progression, Gene Silencing, MicroRNAs, Atherosclerosis, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
