MicroRNA-21 mediates the rapamycin-induced suppression of endothelial proliferation and migration

Rapamycin suppresses endothelial proliferation and migration, which leads to delayed re-endothelialization in the rapamycin-eluted stents that are used in coronary heart disease patients. Because microRNAs (miRs) play important roles in endothelial angiogenesis, we tested the hypothesis that rapamycin induces endothelial suppression, partly through pathways that involve miRs. Rapamycin treatment increased the expression of miR-21 in HUVECs. The downregulation of miR-21 by inhibitors abolished the negative effects of rapamycin on endothelial cell growth and mobility. RhoB was confirmed as a direct target gene of miR-21. Knockdown of Raptor by siRNA mimicked the effects of rapamycin on miR-21 expression. Our study provides a new explanation of the mechanism of rapamycin-mediated inhibition of endothelial proliferation and migration. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.