MicroRNA-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion

J Soh, J Iqbal, J Queiroz, C Fernandez-Hernando… - Nature medicine, 2013 - nature.com
J Soh, J Iqbal, J Queiroz, C Fernandez-Hernando, MM Hussain
Nature medicine, 2013nature.com
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 …
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.
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