title: Hypoxia/Hypoxemia-Induced activation of the procoagulant pathways and the pathogenesis of ischemia-associated thrombosis.
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.
authors.affiliation: Departments of Physiology and Cellular Biophysics, Surgery and Medicine, College of Physicians and Surgeons of Columbia University, New York, NY, USA. djp5@columbia.edu
authors.forename: S F
authors.initials: SF
authors.lastname: Yan
authors.forename: N
authors.initials: N
authors.lastname: Mackman
authors.forename: W
authors.initials: W
authors.lastname: Kisiel
authors.forename: D M
authors.initials: DM
authors.lastname: Stern
authors.forename: D J
authors.initials: DJ
authors.lastname: Pinsky
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D006801:Humans; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology*; D007511:Ischemia / Q000150:complications*; D013927:Thrombosis / Q000209:etiology*