rapamycin regulates the expression and activity of krüppel-like transcription factor 2 in human umbilical vein endothelial cells雷帕霉素调节kruppel-like转录因子的表达和活动2人类脐静脉内皮细胞.pdfVIP

Rapamycin Regulates the Expression and Activity of ¨ Kruppel-Like Transcription Factor 2 in Human Umbilical Vein Endothelial Cells Qian Ma, Xiaomin Nie, Miao Yu, Zhijian Wang, Shiwei Yang, Dean Jia, Yujie Zhou* Department of Cardiology, Beijing Anzhen Hospital Affiliated to the Capital Medical University, Beijing, China Abstract Background: Although rapamycin has been reported to increase procoagulants and decrease anticoagulants in human umbilical vein endothelial cells (HUVECs), there is no significant difference in the incidence of stent thrombosis between ¨ patients with drug-eluting stents (DESs) and those with bare metal stents (BMSs). Kruppel-like transcription factor 2 (KLF2) has been identified as a key regulator of endothelial antithrombotic function. We hypothesized that rapamycin might induce the expression and activity of KLF2, thereby counteracting coronary endothelial dysfunction induced by DESs. Methods and Results: Expression of KLF2, tissue factor (TF) and endothelial NO synthase (eNOS) were assessed in HUVECs treated with rapamycin at concentrations of 2, 20, 200 and 2000 ng/ml for 24 and 48 hours without or with thrombin. Rapamycin strongly induced the expression and activity of KLF2 in high dose groups (p,0.01). Compared with control group, the expression of TF was increased by rapamycin, which inhibited the expression of eNOS after treating for 24 hours (p,0.01). Furthermore, small-interfering RNA–mediated knockdown of KLF2 strongly magnified the ability of rapamycin to induce TF and reduce eNOS accumulation in HUVECs. Conclusions: Rapamycin-dependent induction of KLF2 might partly counteract coronary endothelial dysfunction and thereby pr