title: Small RNA overcomes the challenges of therapeutic targeting of microsomal triglyceride transfer protein.
abstract: The plasma level of apolipoprotein B (apoB) is among the strongest risk factors for coronary artery disease. Microsomal triglyceride transfer protein (MTP) plays a key role in the lipidation of nascent apoB and the secretion of apoB-containing lipoproteins enriched with triglycerides and is thus a promising target for the treatment of hyperlipidemia. Yet, the development of MTP inhibitors to lower plasma lipid concentrations has been hindered by adverse effects on hepatic steatosis. A study recently published in Nature Medicine identifies microRNA-30c (miR-30c) as a potent repressor of MTP that controls plasma apoB-containing lipoprotein levels, in addition to decreasing hepatic lipid synthesis through direct targeting of lysophosphatidylglycerol acyltransferase 1 (LPGAT1). These findings identify miR-30c as a novel therapeutic target that coordinately reduces lipid biosynthesis and lipoprotein secretion to suppress circulating apoB lipoproteins, while sparing the liver from steatosis.
authors.affiliation: From the Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN (K.C.V.); and Marc and Ruti Bell Vascular Biology and Disease Program, Department of Medicine, New York University School of Medicine, New York, NY (K.J.M.).
authors.forename: Kasey C
authors.initials: KC
authors.lastname: Vickers
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Moore
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000378:metabolism*; D050155:Lipogenesis / Q000235:genetics*; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000502:physiology*
chemical_list: D008074:Lipoproteins; D035683:MicroRNAs