Description
Plasminogen Activator Inhibitor-1 (PAI-1, Serpin E1) is a member of the serpin family of serine protease inhibitors and is the primary inhibitor of urokinase and tissue plasminogen activator (tPA) (1-2). It is also a major regulator of fibrinolysis and an important component of the acute phase response, the coordinated systemic reaction of an organism to tissue injury (3). PAI-1 is expressed predominantly in adipose, liver and vascular tissues and is also produced by certain tumor cells. It can also specifically bind vitronectin (VTN) to form a stable active complex with an increased circulatory half life relative to free PAI-1 (4). Elevated levels of PAI-1 are associated with obesity, diabetes and cardiovascular disease, and increased production of PAI-1 is induced by various obesity related factors such as TNFα, glucose, insulin, and very-low-density lipoprotein. The obesity related elevation of PAI-1 levels along with the consequential deficiency in plasminogen activators, can lead directly to increased risk of thrombosis and other coronary diseases. Accordingly, PAI-1 has been implicated as an important molecular link between obesity and coronary disease (5). PAI1 deficiency may represent an inherited autosomal recessive bleeding disorder (6)