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Regulation of Tissue Plasminogen Activator Expression

1989; Annual Reviews; Volume: 51; Issue: 1 Linguagem: Inglês

10.1146/annurev.ph.51.030189.001333

1545-1585

Robert D. Gerard, R S Meidell,

Blood properties and coagulation

Widespread interest in the biology of the fibrinolytic system has developed with the recognition of the role of intravascular thrombosis in the pathogene­ sis of human disease. The therapeutic application of thrombolytic agents is a result of the rapid evolution of our understanding of the biochemistry and physiological importance of this system. In reviewing the regulation of tissue plasminogen activator expression, we emphasize the role of this system in thrombolysis and include within regulated expression the control of enzymatic activity. No attempt is made to review comprehensively the literature con­ cerning plasminogen, plasminogen activators, their respective inhibitors, or the array of biological processes in which these proteins are involved. Instead, the reader is referred to several prior reviews (13, 21, 26, 37, 78, 117) for detailed discussions of these topics. Fibrin forms the structural skeleton of a thrombus, and enzymatic degrada­ tion of fibrin by the serine protease plasmin is the basis of thrombolysis. Plasmin is derived from the inactive circulating zymogen plasminogen by specific proteolytic cleavage of the single-chain precursor to a disulfide­ linked, two-chain, catalytically active form in a process termed plasminogen activation. While several proteases are capable of activating plasminogen with low efficiency, specific plasminogen activators (PA) , urinary PA (u-PA) and tissue PA (t-PA), have been identified. Because of its high catalytic activity for the conversion of plasminogen to plasmin and the selectivity of this process for fibrin surfaces, t-PA appears to