| MicroRNA modulation of cholesterol homeostasis. | |
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MedLine Citation:
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PMID: 22011750 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although the roles of the sterol response element binding protein-1 (SREBP1) and SREBP2 transcription factors in regulating fatty acid and cholesterol synthesis and uptake have been known for some time, it was recently discovered that 2 related microRNAs (miRs), miR-33a and miR-33b, are embedded in these genes. Studies indicate that miR-33a and miR-33b act with their host genes, Srebp2 and Srebp1, respectively, to reciprocally regulate cholesterol homeostasis and fatty acid metabolism in a negative feedback loop. miR-33 has been shown to posttranscriptionally repress key genes involved in cellular cholesterol export and high-density lipoprotein metabolism (Abca1, Abcg1, Npc1), fatty acid oxidation (Crot, Cpt1a, Hadhb, Ampk), and glucose metabolism (Sirt6, Irs2). Delivery of inhibitors of miR-33 in vitro and in vivo relieves repression of these genes, resulting in upregulation of the associated metabolic pathways. In mouse models, miR-33 antagonism has proven to be an effective strategy for increasing plasma high-density lipoprotein cholesterol and fatty acid oxidation and protecting from atherosclerosis. These exciting findings have opened up promising new avenues for the development of therapeutics to treat dyslipidemia and other metabolic disorders. |
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Authors:
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Carlos Fernández-Hernando; Kathryn J Moore |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 31 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-10-20 Completed Date: 2012-01-23 Revised Date: 2012-03-12 |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 2378-82 Citation Subset: IM |
Affiliation:
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Department of Medicine, Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY, USA. carlos.fernandez-hernando@nyumc.org |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cholesterol / metabolism* Fatty Acids / metabolism Glucose / metabolism Humans Mice MicroRNAs / physiology* Models, Animal |
| Grant Support | |
ID/Acronym/Agency:
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R01-AG020255/AG/NIA NIH HHS; R01-HL106063/HL/NHLBI NIH HHS; R01-HL107953/HL/NHLBI NIH HHS; R01-HL108182/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids; 0/MIRN33 microRNA, human; 0/MicroRNAs; 50-99-7/Glucose; 57-88-5/Cholesterol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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