Mechanisms of physiological fibrinolysis.
The fibrinolytic system comprises an inactive proenzyme, plasminogen, that is converted by plasminogen activators to the active enzyme, plasmin, which degrades fibrin. Two immunologically distinct plasminogen activators (PA) have been identified: tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). t-PA mediated plasminogen activation is mainly involved in the dissolution of fibrin in the circulation, whereas u-PA mediated plasminogen activation mainly plays a role in pericellular proteolysis. Plasminogen activation is regulated by specific molecular interactions between its main components, such as binding of plasminogen and t-PA to fibrin, or to specific cellular receptors resulting in enhanced plasminogen activation, inhibition of t-PA and u-PA by plasminogen activator inhibitors (PAI) and inhibition of plasmin by alpha 2-antiplasmin. Controlled synthesis and release of PAs and PAIs primarily from endothelial cells also contributes to the regulation of physiological fibrinolysis. The lysine binding sites situated in the kringle structures of plasminogen play a crucial role in the regulation of fibrinolysis by modulating its binding to fibrin and to cell surfaces, and by controlling the inhibition rate of plasmin by alpha 2-antiplasmin.
Lijnen
H R
HR
Center for Molecular and Vascular Biology, K.U. Leuven, Belgium.
Collen
D
D
D005341:Fibrinolysin / Q000037:antagonists & inhibitors / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D010958:Plasminogen / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000378:metabolism / Q000494:pharmacology; D000979:alpha-2-Antiplasmin / Q000494:pharmacology
D017395:Plasminogen Activator Inhibitor 1; D000979:alpha-2-Antiplasmin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin