E0520 Statin effects in stent thrombosis induced by rapamycin releasing from drug-eluting stents through KrÜppel-Like Factor 2 overexpression. (17th November 2010)

• Record Type: Journal Article
• Authors: Qian, Ma; Yujie, Zhou; Xiaomin, Nie; Miao, Yu; Fei, Gao; Zhijian, Wang; Bin, Nie; Zhenxian, Yan; Hailong, Ge; Dean, Jia; Shiwei, Yang; Xiaoli, Liu; Hongya, Han; Bin, Hu
• Is Part Of: Heart. Volume 96(2010)Supplement 3
• Page Start: A161
• Page End: A162
• Publication Date: 2010-11-17
• Subjects: Endothelium -- thrombosis -- stents -- signal transduction -- myocardial infarction; Heart -- Diseases -- Treatment -- Periodicals; Cardiology -- Periodicals; 616.12
• DOI: 10.1136/hrt.2010.208967.520
• Languages: English
• ISSNs: 1355-6037

Abstract

Abstract : Objects: As we studied before, rapamycin released from drug-eluting stents (DESs) affected the antithrombogenic function of endothelial cells through Krüppel-Like Factor 2 (KLF2) decrease. However, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are known to modulate endothelial function by inducing KLF2. Here we report that statin-induced expression of KLF2 can reverse stent thrombosis. Methods: We observed the effect of rapamycin on expression of KLF2, endothelial NO synthase (eNOS), tissue-plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1) and tissue factor (TF) in Human Umbilical Vein Endothelial Cells (HUVECs). And then KLF2 mRNA was induced by treatment with multiple statins in a concentration-dependent manner. The mRNA and protein were mensurated by RT-PCR and Western Blot Analysis. Furthermore, activation of KLF2 was evaluated by Electrophoretic Mobility Shift Assay (EMSA). Results: Rapamycin made the expression and activation of KLF2 strongly reduce by 75.6% and 78.2% so as to induce long-term coronary endothelial dysfunction. In HUVECs, rapamycin made basal eNOS and t-PA decrease by 80% and 87.8%, while making basal PAI-1 and TF increase by 2.5 and 1.5-fold. After treatment by statins (especially lovastatin), the expression of KLF2 was increased by 3.8-fold nearly reversing to normal state. Conclusions: Taken together, these observations indicate that statin-dependent induction of KLF2 provides a new treatment for stent thrombosis induced by rapamycin releasing from drug-eluting stents.