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Semin Vasc Med 2003; 03(2): 193-198
DOI: 10.1055/s-2003-40677
Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

The Role of the Tissue Factor-Thrombin Pathway in Cardiac Ischemia-Reperfusion Injury

Nigel Mackman
  • Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA
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Publication History

Publication Date:
18 July 2003 (online)

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ABSTRACT

This article focuses on the role of the tissue factor (TF)-thrombin pathway in cardiac ischemia-reperfusion (I/R) injury. We and others have used rabbit models of cardiac I/R injury to show that anti-TF therapy prevents the transient decrease in regional myocardial blood flow, reduces platelet and fibrin(ogen) accumulation, and reduces infarct size. At present, the mechanism by which TF-initiated coagulation contributes to myocardial injury is not established. Inhibition of TF may decrease intravascular fibrin deposition and thrombosis. However, immunohistochemical studies demonstrated that fibrin deposition was predominantly within the myocardium and depletion of fibrinogen did not reduce infarct size. In contrast, inhibition of thrombin reduced infarct size to a similar extent as anti-TF therapy. We propose that the TF-thrombin pathway may contribute to myocardial injury by an additional mechanism that is not dependent on fibrin deposition but involves activation of protease activated receptor 1 (PAR-1) on vascular endothelial cells and cardiac myocytes. Anti-TF therapy would inhibit both thrombin-dependent fibrin deposition and thrombin-dependent PAR-1 signaling.

KEYWORDS

Cardiac ischemia-reperfusion injury - tissue factor - coagulation - protease activated receptor

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