Plasminogen activator inhibitor 1, fibrin, and the vascular response to injury.
Intravascular fibrin deposition is believed to play an important role in the development of intimal hyperplasia, which is a hallmark of several human vascular disorders, including atherosclerosis and restenosis after balloon angioplasty. Plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor or tissue- and urinary-type plasminogen activator, plays a key role in fibrin homeostasis by controlling plasmin formation. PAI-1 may also modulate vascular pathology via alternative pathways, such as inhibiting activated protein C and altering interactions between vascular smooth muscle cells and the extracellular matrix. The diverse functional profile of PAI-1 likely accounts for the variation observed in its impact on intimal hyperplasia in different disease models. This review examines recent studies addressing the vascular function of PAI-1, and those assessing the role of fibrin as a downstream mediator of PAI-1's effects.
Fay
William P
WP
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA. wfay@umich.edu
D000818:Animals; D003324:Coronary Artery Disease / Q000378:metabolism*; D004195:Disease Models, Animal; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D051379:Mice; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*
D017395:Plasminogen Activator Inhibitor 1; D005337:Fibrin