microRNA-30c reduces plasma cholesterol in homozygous familial hypercholesterolemic and type 2 diabetic mouse models

• Published in: Journal of lipid research 2018-01, Vol.59 (1), p.144-154
• Main Authors: Irani, Sara, Iqbal, Jahangir, Antoni, W. James, Ijaz, Laraib, Hussain, M. Mahmood
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Apolipoprotein E; Arteriosclerosis; Atherosclerosis; Cholesterol; Cholesterol - blood; Creatine; Creatine kinase; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - genetics; Disease Models, Animal; Humans; Hypercholesterolemia; Hypercholesterolemia - blood; Hypercholesterolemia - genetics; Lipids; Lipoproteins (very low density); Low density lipoprotein; Low density lipoprotein receptors; Metabolic disorders; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; micro-ribonucleic acid-30c; MicroRNAs; MicroRNAs - metabolism; miRNA; Protein biosynthesis; Receptors, LDL - deficiency; Receptors, LDL - metabolism; Rodents; Steatosis
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M081299

High plasma cholesterol levels are found in several metabolic disorders and their reductions are advocated to reduce the risk of atherosclerosis. A way to lower plasma lipids is to curtail lipoprotein production; however, this is associated with steatosis. We previously showed that microRNA (miR)-30c lowers diet-induced hypercholesterolemia and atherosclerosis in C57BL/6J and Apoe−/− mice. Here, we tested the effect of miR-30c on plasma lipids, transaminases, and hepatic lipids in different mouse models. Hepatic delivery of miR-30c to chow-fed leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) hypercholesterolemic and hyperglycemic mice reduced cholesterol in total plasma and VLDL/LDL by ∼28% and ∼25%, respectively, without affecting triglyceride and glucose levels. And these mice had lower plasma transaminases and creatine kinase activities than controls. Moreover, miR-30c significantly lowered plasma cholesterol and atherosclerosis in Western diet-fed Ldlr−/− mice with no effect on plasma triglyceride, glucose, and transaminases. In these studies, hepatic lipids were similar in control and miR-30c-injected mice. Mechanistic studies showed that miR-30c reduced hepatic microsomal triglyceride transfer protein activity and lipid synthesis. Thus miR-30c reduced plasma cholesterol in several diet-induced and diabetic hypercholesterolemic mice. We speculate that miR-30c may be beneficial in lowering plasma cholesterol in different metabolic disorders independent of the origin of hypercholesterolemia.