Noncoding RNAs in vascular inflammation and atherosclerosis: recent advances toward therapeutic applications.

Abstract

We here highlight recent studies that in vivo demonstrate an involvement of microRNAs in atherosclerotic lesion formation and provide important preclinical evidence of their therapeutic targeting in atherosclerosis, with a particular focus on endothelial cells and macrophages. We also briefly discuss the emerging role of long noncoding RNAs herein. Noncoding RNAs have received considerable attention as regulators of different cell types and functions that dictate the inflammatory response in atherosclerosis. In particular, microRNAs have emerged to control endothelial cell functions by acting as mechanosensors that are regulated by flow, determinants of inflammation in the context of cytokine exposure and hypercholesterolemia and guardians of endothelial homeostasis. In addition, microRNAs control macrophage-driven cytokine production and polarization, and regulate cholesterol metabolism and foam cell formation. By these (cell specific) effects, microRNAs contain or drive atherosclerotic lesion formation and progression in animal models of disease and can be harnessed for therapeutic targeting. Given their multifaceted and specific contribution to vascular inflammation and atherosclerosis, and proven amenability for successful modulation in preclinical murine models of atheroscleorosis and large animal studies, miRNAs appear as promising therapeutic targets for treating atherosclerosis.