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: James Soh, Jahangir Iqbal, Joyce Queiroz, Carlos Fernandez-Hernando, M Mahmood Hussain
• Journal: Nature medicine (Nat Med) Vol. 19 Issue 7 Pg. 892-900 (Jul 2013) ISSN: 1546-170X [Electronic] United States
• PMID: 23749231 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Carrier Proteins
• Lipoproteins
• MicroRNAs
• Mirn30d microRNA, mouse
• microsomal triglyceride transfer protein

Topics

• Animals
• Atherosclerosis (genetics, metabolism)
• COS Cells
• Carrier Proteins (genetics, metabolism)
• Cell Line, Tumor
• Chlorocebus aethiops
• Down-Regulation (genetics)
• Female
• Humans
• Hyperlipidemias (genetics, metabolism)
• Lipogenesis (genetics)
• Lipoproteins (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• MicroRNAs (genetics, metabolism, physiology)