Tissue plasminogen activator (TPA, tPA)

[MIM*173370] (1) a naturally occurring thrombolytic serine protease that catalyzes the conversion of plasminogen to plasmin; (2) a genetically engineered protein used as a thrombolytic agent in myocardial infarction, stroke, and peripheral vascular thrombosis.TPA is a single-chain glycoprotein with a molecular weight of about 70 kD. Released by endothelial cells at sites of vascular injury, it modulates thrombogenesis by converting fibrin-bound plasminogen to plasmin, cleaving the arginine-valine bond of plasminogen at the 560-561 position. As a result, fibrin strands in a clot are chemically degraded and platelet adhesion and aggregation are inhibited. TPA has little effect on plasminogen in the absence of fibrin, and its release does not significantly reduce systemic concentrations of fibrinogen. Alteplase, a synthetic TPA produced by recombinant DNA technology, improves outcomes when administered intravenously in acute myocardial infarction and in selected cases of stroke, pulmonary embolism, and peripheral ischemia due to thrombosis. It has a circulating half-life of only 4-6 minutes, but persists in clots up to 7 hours. see thrombolytic therapy