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Thromb Res. 2010 May;125(5):377-81. doi: 10.1016/j.thromres.2009.11.034. Epub 2010 Jan 15.

Plasminogen activator inhibitor-1 is an aggregate response factor with pleiotropic effects on cell signaling in vascular disease and the tumor microenvironment.

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  • 1Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC 27599-7035, USA.

Abstract

In hemostasis, the serine protease inhibitor (serpin) plasminogen activator inhibitor-1 (PAI-1) functions to stabilize clots via inhibition of tissue plasminogen activator (tPA) with subsequent inhibition of fibrinolysis. In tissues, PAI-1 functions to inhibit extracellular matrix degradation via inhibition of urokinase plasminogen activator (uPA). Elevated levels of PAI-1 in the vasculature and in tissues have long been known to be associated with thrombosis and fibrosis, respectively. However, there is emerging evidence that PAI-1 may participate in the pathophysiology of a number of diseases such as atherosclerosis, restenosis, and cancer. In many of these disease states, the canonical view of PAI-1 as an inhibitor of tPA and uPA cannot fully account for a mechanism whereby PAI-1 contributes to the disease. In these cases, one must consider recent data, which indicates PAI-1 can directly promote pro-proliferative and anti-apoptotic signaling in a variety of cell types. Given the wide variety of inflammatory, hormonal, and metabolic signals that increase PAI-1 expression, it is important to consider mechanisms by which PAI-1 can directly participate in disease etiology.

Copyright (c) 2010 Elsevier B.V. All rights reserved.

PMID:
20079523
[PubMed - indexed for MEDLINE]
PMCID:
PMC2860057
Free PMC Article
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