論文

査読有り
2003年3月

Pitavastatin-induced Thrombomodulin expression by endothelial cells acts via inhibition of small G proteins of the Rho family

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
  • K Masamura
  • ,
  • K Oida
  • ,
  • H Kanehara
  • ,
  • J Suzuki
  • ,
  • S Horie
  • ,
  • H Ishii
  • ,
  • Miyamori, I

23
3
開始ページ
512
終了ページ
517
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1161/01.ATV.0000060461.64771.F0
出版者・発行元
LIPPINCOTT WILLIAMS & WILKINS

Objective-3-Hydroxyl-3-methyl coenzyme A reductase inhibitors (statins) can function to protect the vasculature in a manner that is independent of their lipid-lowering activity. The main feature of the antithrombotic properties of endothelial cells is an increase in the expression of thrombomodulin (TM) without induction of tissue factor (TF) expression. We investigated the effect of statins on the expression of TM and TF by endothelial cells.
Methods and Results-The incubation of endothelial cells with pitavastatin led to a concentration-and time-dependent increase in cellular TM antigen and mRNA levels. In contrast, the expression of TF mRNA was not induced under the same conditions. A nuclear run-on study revealed that pitavastatin accelerates TM transcription rate. The stimulation of TM expression by pitavastatin was prevented by either mevalonate or geranylgeranylpyrophosphate. Specific inhibition of geranylgeranyltransferase-I and Rac/Cdc42 by GGTI-286 and Clostridium sordellii lethal toxin, respectively, enhanced TM expression, whereas inactivation of Rho by Clostridium botulinum C3 exoenzyme was ineffective.
Conclusions-Statins regulate TM expression via inhibition of small G proteins of the Rho family; Rac/Cdc42. A statin-mediated increase in TM expression by endothelial cells may contribute to the beneficial effects of statins on endothelial function.


リンク情報
DOI
https://doi.org/10.1161/01.ATV.0000060461.64771.F0
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000181549400027&DestApp=WOS_CPL
ID情報
  • DOI : 10.1161/01.ATV.0000060461.64771.F0
  • ISSN : 1079-5642
  • Web of Science ID : WOS:000181549400027

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