title: MicroRNA-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion.
abstract: Hyperlipidemia is a risk factor for various cardiovascular and metabolic disorders. Overproduction of lipoproteins, a process that is dependent on microsomal triglyceride transfer protein (MTP), can contribute to hyperlipidemia. We show that microRNA-30c (miR-30c) interacts with the 3' untranslated region of MTP mRNA and induces its degradation, leading to reductions in MTP activity and in apolipoprotein B (APOB) secretion. miR-30c also reduces lipid synthesis independently of MTP. Hepatic overexpression of miR-30c reduced hyperlipidemia in Western diet-fed mice by decreasing lipid synthesis and the secretion of triglyceride-rich ApoB-containing lipoproteins and decreased atherosclerosis in Apoe(-/-) mice. Furthermore, inhibition of hepatic miR-30c by anti-miR-30c increased hyperlipidemia and atherosclerosis. Therefore, miR-30c coordinately reduces lipid biosynthesis and lipoprotein secretion, thereby regulating hepatic and plasma lipid concentrations. Raising miR-30c levels might be useful in treating hyperlipidemias and associated disorders.
authors.affiliation: School of Graduate Studies, Molecular and Cell Biology Program, State University of New York Downstate Medical Center, Brooklyn, New York, USA.
authors.forename: James
authors.initials: J
authors.lastname: Soh
authors.forename: Jahangir
authors.initials: J
authors.lastname: Iqbal
authors.forename: Joyce
authors.initials: J
authors.lastname: Queiroz
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez-Hernando
authors.forename: M Mahmood
authors.initials: MM
authors.lastname: Hussain
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism*; D050155:Lipogenesis / Q000235:genetics*; D008074:Lipoproteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D008074:Lipoproteins; D035683:MicroRNAs; C534715:Mirn30d microRNA, mouse; C106092:microsomal triglyceride transfer protein