Plasminogen activator inhibitor-1 is an aggregate response factor with pleiotropic effects on cell signaling in vascular disease and the tumor microenvironment.
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.
Gramling
Mark W
MW
Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC 27599-7035, USA.
Church
Frank C
FC
D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000276:immunology*; D017395:Plasminogen Activator Inhibitor 1 / Q000276:immunology*; D010974:Platelet Aggregation / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D014652:Vascular Diseases / Q000276:immunology*
D017395:Plasminogen Activator Inhibitor 1