title: Rapamycin regulates the expression and activity of Krüppel-like transcription factor 2 in human umbilical vein endothelial cells.
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). Krüppel-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.
  
  
  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 provided a novel molecular target to prevent stent thrombosis induced by DESs.
authors.affiliation: Department of Cardiology, Beijing Anzhen Hospital Affiliated to the Capital Medical University, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ma
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Nie
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Wang
authors.forename: Shiwei
authors.initials: S
authors.lastname: Yang
authors.forename: Dean
authors.initials: D
authors.lastname: Jia
authors.forename: Yujie
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D024202:Electrophoretic Mobility Shift Assay; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D020123:Sirolimus / Q000494:pharmacology*; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism / Q000517:prevention & control
chemical_list: D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; D013925:Thromboplastin; D052250:Nitric Oxide Synthase Type III; D020123:Sirolimus