title: MicroRNA-21 mediates the rapamycin-induced suppression of endothelial proliferation and migration.
abstract: 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.
authors: Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou 310016, Zhejiang Province, PR China.
authors: Chongying
authors: C
authors: Jin
authors: Yanbo
authors: Y
authors: Zhao
authors: Lu
authors: L
authors: Yu
authors: Shengjie
authors: S
authors: Xu
authors: Guosheng
authors: G
authors: Fu
mesh_terms: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D054855:Drug-Eluting Stents / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020868:Gene Silencing; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D035683:MicroRNAs / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D000076223:Regulatory-Associated Protein of mTOR; D020123:Sirolimus / Q000009:adverse effects / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects; D020743:rhoB GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D000900:Anti-Bacterial Agents; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C463659:RPTOR protein, human; D000076223:Regulatory-Associated Protein of mTOR; D020743:rhoB GTP-Binding Protein; D020123:Sirolimus