Hypoxia/hypoxemia-induced activation of the procoagulant pathways and the pathogenesis of ischemia-associated thrombosis

被引:146
|
作者
Yan, SF
Mackman, N
Kisiel, W
Stern, DM
Pinsky, DJ
机构
[1] Columbia Univ Coll Phys & Surg, Dept Physiol & Cellular Biophys, New York, NY 10032 USA
[2] Columbia Univ Coll Phys & Surg, Dept Surg, New York, NY 10032 USA
[3] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA
[4] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
[5] Scripps Res Inst, Dept Vasc Biol, La Jolla, CA 92037 USA
[6] La Jolla Canc Res Fdn, La Jolla, CA 92037 USA
[7] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA
[8] Univ New Mexico, Sch Med, Dept Biochem, Albuquerque, NM 87131 USA
关键词
tissue factor; hypoxia; ischemia; Egr-1; PAI-1;
D O I
10.1161/01.ATV.19.9.2029
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 never 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.
引用
收藏
页码:2029 / 2035
页数:7
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