title: MicroRNAs regulating lipid metabolism in atherogenesis.
abstract: MicroRNAs have emerged as important post-transcriptional regulators of lipid metabolism, and represent a new class of targets for therapeutic intervention. Recently, microRNA-33a and b (miR-33a/b) were discovered as key regulators of metabolic programs including cholesterol and fatty acid homeostasis. These intronic microRNAs are embedded in the sterol response element binding protein genes,  SREBF2  and  SREBF1, which code for transcription factors that coordinate cholesterol and fatty acid synthesis. By repressing a variety of genes involved in cholesterol export and fatty acid oxidation, including  ABCA1,  CROT,  CPT1,  HADHB  and  PRKAA1, miR-33a/b act in concert with their host genes to boost cellular sterol levels. Recent work in animal models has shown that inhibition of these small non-coding RNAs has potent effects on  lipoprotein metabolism, including increasing plasma high-density lipoprotein (HDL) and reducing very low density lipoprotein (VLDL) triglycerides. Furthermore, other microRNAs are being discovered that also target the ABCA1 pathway, including miR-758, suggesting that miRNAs may work cooperatively to regulate this pathway. These exciting findings support the development of microRNA antagonists as potential therapeutics for the treatment of dyslipidaemia, atherosclerosis and related metabolic diseases.
authors.affiliation: Department of Medicine and Cell Biology, New York University School of Medicine, New York, New York, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Rayner
authors.forename: C
authors.initials: C
authors.lastname: Fernandez-Hernando
authors.forename: K J
authors.initials: KJ
authors.lastname: Moore
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D008079:Lipoproteins, VLDL; D008099:Liver / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics*; D014280:Triglycerides
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D005227:Fatty Acids; D008075:Lipoproteins, HDL; D008079:Lipoproteins, VLDL; C531907:MIRN122 microRNA, human; C550416:MIRN33a microRNA, human; C569441:MIRN758 microRNA, human; D035683:MicroRNAs; C550417:Mirn33 microRNA, mouse; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D002784:Cholesterol