Abstract 115: Microrna-30c Reduces Hyperlipidemia and Atherosclerosis by Decreasing Lipid Synthesis and Lipoprotein Secretion

Abstract

Hyperlipidemia is a risk factor for various cardiovascular and metabolic disorders. Overproduction of lipoproteins, a process critically dependent on microsomal triglyceride transfer protein (MTP), can contribute to hyperlipidemia. We have shown that hepatic over expression of miR-30c reduces MTP mRNA, protein and activity. Further, MTP mRNA is degraded faster due to the binding of miR-30c to its 3[[Unable to Display Character: ΄]]-UTR. miR-30c lowers plasma cholesterol by reducing production of triglyceride-rich apoB-containing lipoproteins; a phenotype most likely secondary to lower MTP expression. It also reduces de novo lipogenesis by targeting other genes such as LPGAT1. Additionally, atherosclerotic plaques are smaller in Apoe -/- mice expressing miR-30c. Taken together, we have provided evidence that high miR-30c levels reduce plasma lipids and atherosclerosis and avoids steatosis by regulating different sets of genes.