Defects in homeostatic regulation of cholesterol and fatty acids are associated with major cardiometabolic risk factors that are prevalent in type 2 diabetes and atherosclerotic cardiovascular disease. Regulatory input is found at many levels; however, recent findings have revealed pivotal roles for small non-coding RNAs (microRNAs) of the endogenous RNA interference pathway in post-transcriptional control of major regulatory mechanisms underpinning cholesterol and energy homeostasis. In addition, aberrant expression of microRNAs has been implicated in marked pathophysiologic events contributing to the progression and development of atherosclerosis, including loss of endothelial integrity, vascular smooth muscle cell proliferation, neointimal hyperplasia, and foam cell formation. This review surveys the impact of microRNA-mediated regulation in biological processes governing the cholesterol/lipoprotein metabolism, fatty acid β-oxidation (eg by miR-122 and miR-33), and endothelial dysfunction related to atherosclerosis. Given the current advances in microRNA-based technologies, the clinical potential of microRNAs as novel therapeutic targets is highlighted as new alternative strategies to ameliorate cardiometabolic diseases.
