Flow mediation of endothelial-smooth muscle cell interaction through microRNAs (696.4)

In atherosclerotic lesions, synthetic smooth muscle cells (sSMCs) induce aberrant microRNA (miR) profiles in endothelial cells (ECs) under flow stagnation. Increase in shear stress results in favorable miR modulation to mitigate sSMC-induced inflammation. The objective of this study was to address the role of miRs in sSMC-induced EC inflammation and its inhibition by shear stress. Co-culturing ECs with sSMCs under static condition caused initial increases of four anti-inflammatory miRs (146a/708/451/98) in ECs followed by decreases below the basal levels at 7 days; the increases for miR-146a/708 peaked at 24 h and those for miR-451/98 lasted for only 6-12 h. Shear stress (12 dynes/cm2) to ECs co-cultured with sSMCs for 24 h augments the expression of these four miRs. In vivo, these four miRs are not expressed in neointimal ECs in injured arteries under flow stagnation, but become highly expressed under physiological levels of flow. MiR-146a, -708, -451, and -98 target interleukin (IL)-1 receptor-associate...