title: Rapamycin affects tissue plasminogen activator and plasminogen activator inhibitor I expression: a potential prothrombotic mechanism of drug-eluting stents.
abstract: Although drug-eluting stents (DESs) can decrease the risk of restenosis, this benefit is tempered by a possible increased risk of in-stent thrombosis. We assessed the effects of rapamycin on human umbilical vein endothelial cells (HUVECs) to identify the alterations in gene expression associated with thrombosis. Expression of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) was assessed in HUVECs treated with rapamycin (final concentrations: 1, 10, 100, and 1000 ng/mL) for 24 and 48 hours. Incubation of HUVECs with rapamycin strongly reduced the expression of t-PA in a concentration-dependant manner (P < .05 to < .01). However, the expression of PAI-1 was induced by rapamycin (P < .05 to < .01). The increase in PAI-1 induction was up to 3.3-fold. In conclusion, rapamycin inhibited t-PA and induced PAI-1 expression in HUVECs. This effect may contribute to in-stent thrombosis associated with DESs.
authors: Department of Cardiology, Beijing Anzhen Hospital Affiliated to the Capital Medical University, Beijing, China.
authors: Qian
authors: Q
authors: Ma
authors: Yujie
authors: Y
authors: Zhou
authors: Xiaomin
authors: X
authors: Nie
authors: Miao
authors: M
authors: Yu
authors: Fei
authors: F
authors: Gao
authors: Zhijian
authors: Z
authors: Wang
authors: Hailong
authors: H
authors: Ge
authors: Dean
authors: D
authors: Jia
authors: Shiwei
authors: S
authors: Yang
authors: Xiaoli
authors: X
authors: Liu
authors: Hongya
authors: H
authors: Han
authors: Bin
authors: B
authors: Hu
authors: Hua
authors: H
authors: Shen
authors: Xiaohan
authors: X
authors: Xu
mesh_terms: D002317:Cardiovascular Agents / Q000633:toxicity*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D054855:Drug-Eluting Stents; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D011474:Prosthesis Design; D012333:RNA, Messenger / Q000378:metabolism; D020123:Sirolimus / Q000633:toxicity*; D013927:Thrombosis / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D002317:Cardiovascular Agents; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C051321:SERPINE1 protein, human; D010959:Tissue Plasminogen Activator; D020123:Sirolimus