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Statin prevents tissue factor expression in human endothelial cells: role of Rho/Rho-kinase and Akt pathways

Masato Eto1, Toshiyuki Kozai, Francesco Cosentino

  • 1Division of Cardiology, CardioVascular Center, University Hospital and University of Zurich, Zurich, Switzerland.

Circulation
|April 17, 2002
PubMed

Insights

Statins inhibit thrombin-induced tissue factor expression in endothelial cells by blocking Rho/Rho-kinase and activating Akt. This clarifies statin mechanisms in acute coronary syndromes.

Area of Science:

  • Cardiovascular Biology
  • Cell Signaling
  • Pharmacology

Background:

  • Tissue factor is crucial for thrombus formation in acute coronary syndromes.
  • Regulatory pathways of tissue factor expression are not fully understood.
  • Statins demonstrate efficacy in treating acute coronary syndromes.

Purpose of the Study:

  • Investigate thrombin-induced tissue factor signaling in human endothelial cells.
  • Determine the inhibitory effects of statins on this pathway.

Main Methods:

  • Utilized human aortic endothelial and smooth muscle cells.
  • Assessed tissue factor expression and activity.
  • Examined the roles of Rho A, p38 MAP kinase, and Akt signaling pathways.
  • Employed specific inhibitors (Y-27632, SB203580, wortmannin) and simvastatin.

Main Results:

  • Simvastatin inhibited thrombin-induced tissue factor expression and activity in a concentration-dependent manner.
  • Simvastatin blocked thrombin-induced Rho A activation but not p38 MAP kinase activation.
  • Thrombin-induced Akt dephosphorylation was inhibited by simvastatin and a Rho-kinase inhibitor.
  • Mevalonate reversed the inhibitory effects of simvastatin.

Conclusions:

  • Thrombin-induced tissue factor expression is regulated by Rho/Rho-kinase, Akt, and p38 MAP kinase pathways.
  • Simvastatin exerts its inhibitory effect by targeting Rho/Rho-kinase and promoting Akt activation.
  • These findings offer novel insights into the therapeutic actions of statins in acute coronary syndromes.
Abstract

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