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Clinical and research medicine: Interventional cardiology
e0520 Statin effects in stent thrombosis induced by rapamycin releasing from drug-eluting stents through KrÜppel-Like Factor 2 overexpression
  1. Ma Qian,
  2. Zhou Yujie,
  3. Nie Xiaomin,
  4. Yu Miao,
  5. Gao Fei,
  6. Wang Zhijian,
  7. Nie Bin,
  8. Yan Zhenxian,
  9. Ge Hailong,
  10. Jia Dean,
  11. Yang Shiwei,
  12. Liu Xiaoli,
  13. Han Hongya,
  14. Hu Bin
  1. Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

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.

  • Endothelium
  • thrombosis
  • stents
  • signal transduction
  • myocardial infarction

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