Effects of HMG-CoA reductase inhibitors on blood coagulation and fibrinolytic regulation factors in the endothelial cell

  • YAMAZAKI Kazumi
    Department of Laboratory Science, School of Health Sciences, Faculty of Medicine, Kanazawa University
  • MORISHITA Eriko
    Department of Laboratory Science, School of Health Sciences, Faculty of Medicine, Kanazawa University
  • HIRANO Kyoko
    Department of Laboratory Science, School of Health Sciences, Faculty of Medicine, Kanazawa University
  • SEKINO Tomonori
    Department of Laboratory Science, School of Health Sciences, Faculty of Medicine, Kanazawa University
  • YOSHIDA Tomotaka
    Department of Central Clinical Laboratory, Kanazawa University Hospital
  • HAYASHI Tomoe
    Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science
  • MIDATE Yasuo
    Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science
  • YAMAZAKI Masahide
    Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science
  • ASAKURA Hidesaku
    Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science
  • NAKAO Shinji
    Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science
  • OHTAKE Shigeki
    Department of Laboratory Science, School of Health Sciences, Faculty of Medicine, Kanazawa University

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Other Title
  • 血管内皮細胞における凝固線溶制御因子の発現に与えるHMG‐CoA還元酵素阻害剤の影響

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Abstract

Recent clinical trials have shown that HMG-CoA reductase inhibitors (statins) reduce the risk of acute coronary events. These beneficial effects are thought to be due not only to lipid-lowering functions, but also to the direct vascular protective activities including antithrombotic properties. The aim of this study was to elucidate the effects of statins on the blood coagulation and fibrinolytic regulation factors in human endothelial cells, in vitro. Human umbilical vein endothelial cells (HUVEC) were incubated with fluvastatin, a liposoluble statin, at 37°C for 24 hours. After extraction of the total RNA, mRNA’s of tissue factor pathway inhibitor (TFPI), thrombomodulin (TM) and plasminogen activator inhibitor type-1 (PAI-1) were individually analyzed by the real-time PCR. Fluvastatin increased mRNA levels of TFPI and TM in a dose-dependent manner, but reduced the induction of PAI-1 mRNA level. The similar effects were observed in the levels of TFPI, TM and PAI-1 antigens in the mediums and cell lysates. Furthermore, effects of fluvastatin on the expression of TFPI, TM and PAI-1 mRNA’s were suppressed by mevalonate and geranylgeranylpyrophosphate (GGPP) but not by farnesylpyrophosphate (FPP). <br>Taken together, these results suggest that statins lead to the acquisition of anticoagulation properties in human endothelial cells in vivo.

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