Abstract
Fibrinolysis is the ultimate outcome of a cascade of enzymatic reactions in which serine proteases such as plasmin, tissue plasminogen activator (tPA), and urokinase plasminogen activator (uPA) are the key players. Plasmin degrades fibrin into soluble fibrin degradation products. The tPA-mediated plasminogen activation is mainly involved in the dissolution of fibrin in the circulating blood whereas the uPA binds to a specific cellular receptor, resulting in an enhanced activation of cell membrane bound plasminogen. These proteases are regulated by serine protease inhibitors (serpins). Serpin-mediated regulation may occur either at the level of plasmin, mainly by α2-antiplasmin (α2-AP) or at the level of the PAs, mainly by plasminogen activator inhibitor -1 (PAI-1). Other serpins may also be involved including plasminogen activator inhibitor -2 and -3 (PAI-2 and PAI-3), protease nexin-1 (PN-1), C1-inhibitor (C1-INH), placental thrombin inhibitor (PTI), neuroserpin, and yukopin. The serpin-protease reactions serve as potential platforms to develop therapeutics for the treatment and prevention of cardiovascular diseases such as thrombosis and hemorrhage. This review will describe key serpins involved in the regulation of fibrinolytic system, particularly α2-AP and PAI-1, with the focus on their biochemical and biophysical aspects, the pathologies related to their dysfunction or deficiency, their therapeutic roles, and their reported cofactors or modulators.
Keywords: Antiplasmin, fibrinolysis, PAI-1, plasmin, serpin, thrombolysis, thrombosis, tPA, uPA.
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