MiR-92a

Abstract

During life, our arteries with their 3 layers, numerous curvatures, branch points, and bifurcations, are continuously exposed to different flow and shear stress conditions. At branch points and bifurcations, especially oscillatory shear stress activates the endothelium, making these arterial sites prone to develop atherosclerosis.1,2 The subendothelial deposition and subsequent modification of lipids, such as low-density lipoprotein (LDL), further enhances this vascular inflammation. Along with endothelial activation, both the innate and adaptive immune system come into play, resulting in further recruitment of leukocytes and formation of atherosclerotic plaques.1,2 Article, see p 434 To keep the development of atherosclerosis under control, our arteries are subjected to a tight regulation to maintain their homeostasis. Regulatory RNAs, including micro-RNAs, are powerful post-transcriptional mediators that control vascular homeostasis, and their deregulation can result in aggravation of endothelial dysfunction and aggravation of vascular disease. Micro-RNAs can therefore be considered as potential novel therapeutics to treat cardiovascular disease.3 In this issue of Circulation Research , Loyer et al4 performed an elegant screening to identify micro-RNAs affecting atherosclerosis, the so-called atheromiRs, in endothelial cells. The authors selected the atheromiRs in in vitro settings using human umbilical vein endothelial cells based on 2 criteria that are highly relevant for the pathogenesis of atherosclerosis: (1) miRs that exhibit a change in expression by exposure to oxidized LDL (oxLDL) under low shear stress and (2) miRs that are not affected by oxLDL exposure under high shear stress conditions. The miR that was most dysregulated and fulfilled these criteria was miR-92a, which was highly expressed in atherosclerosis-prone regions in normocholesterolemic ldlr −/− mice compared with atherosclerosis-resistant regions in these mice. This difference in miR-92a expression was …