Micro-RNAs and High-Density Lipoprotein Metabolism

Abstract

Improved prevention and treatment of cardiovascular diseases is one of the challenges in Western societies, where ischemic heart disease and stroke are the leading cause of death. Early epidemiological studies have shown an inverse correlation between circulating high-density lipoprotein-cholesterol (HDL-C) and cardiovascular diseases. The cardioprotective effect of HDL is because of its ability to remove cholesterol from plaques in the artery wall to the liver for excretion by a process known as reverse cholesterol transport. Numerous studies have reported the role that micro-RNAs (miRNA) play in the regulation of the different steps in reverse cholesterol transport, including HDL biogenesis, cholesterol efflux, and cholesterol uptake in the liver and bile acid synthesis and secretion. Because of their ability to control different aspects of HDL metabolism and function, miRNAs have emerged as potential therapeutic targets to combat cardiovascular diseases. In this review, we summarize the recent advances in the miRNA-mediated control of HDL metabolism. We also discuss how HDL particles serve as carriers of miRNAs and the potential use of HDL-containing miRNAs as cardiovascular diseases biomarkers.

Keywords: atherosclerosis; biomarkers; cardiovascular diseases; cholesterol, HDL; microRNAs.

Figure. miRNA regulation of HDL metabolism and reverse cholesterol transport

Schematic overview of miRNAs involved in the regulation of HDL metabolism and reverse cholesterol transport (RCT). Grey boxes highlight miRNAs which regulate genes that control HDL metabolism and RCT (red boxes). Note that only miRNAs highlighted in red have been demonstrated to influence HDL metabolism in vivo. ABC indicates ATP-binding cassette; SR-BI, scavenger receptor B1 and CYP7A1, cholesterol 7 alpha-hydroxylase. Figure was created using the Servier Medical Art illustration resources (http://www.servier.com).