© 1999 American Heart Association, Inc.
Brief Review |
Hypoxia/Hypoxemia-Induced Activation of the Procoagulant Pathways and the Pathogenesis of Ischemia-Associated Thrombosis
From the Departments of Physiology and Cellular Biophysics, Surgery and Medicine, College of Physicians and Surgeons of Columbia University, New York, NY (S.-F.Y., D.M.S., D.J.P.), the Departments of Immunology and Vascular Biology, The Scripps Research Institute and La Jolla Cancer Research Foundation, La Jolla, CA (N.M.), and the Departments of Pathology and Biochemistry, University of New Mexico School of Medicine, Albuquerque, NM (W.K.).
Correspondence to Dr Shi-Fang Yan/Dr David J. Pinsky, Departments of Physiology and Cellular Biophysics, P&S 17-401, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, New York. E-mail djp5{at}columbia.edu
Abstract—Although oxygen deprivation has long been associated with triggering of the procoagulant pathway and venous thrombosis, blood hypoxemia and stasis by themselves do not lead to fibrin formation. A pathway is outlined through which diminished levels of oxygen activate the transcription factor early growth response-1 (Egr-1) leading to de novo transcription/translation of tissue factor in mononuclear phagocytes and smooth muscle cells, which eventuates in vascular fibrin deposition. The procoagulant response is magnified by concomitant suppression of fibrinolysis by hypoxia-mediated upregulation of plasminogen activator inhibitor-1. These data add a new facet to the biology of thrombosis associated with hypoxemia/stasis and imply that interference with mechanisms causing Egr-1 activation in response to oxygen deprivation might prevent vascular fibrin deposition occurring in ischemia without directly interfering with other pro/anticoagulant pathways.
Key Words: tissue factor • hypoxia • ischemia • Egr-1 • PAI-1
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