Fibrinolysis: Its initiation and regulation |
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Authors: | Nobuo Aoki |
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Affiliation: | (1) First Department of Medicine, Tokyo Medical and Dental University, Tokyo, Japan |
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Abstract: | Fibrinolytic system is one of the major proteolytic pathways in vivo and primarily responsible for dissolution of thrombi. Two enzymes are primarily involved in this proteolytic system; plasminogen activator (PA) and plasmin. Plasmin is formed by a limited proteolysis of plasminogen by PA, which is mainly synthesized by and secreted from vascular endothelial cells. This proteolytic process proceeds physiologically only on the surface of fibrin. Thus, initiation and progression of the fibrinolytic process depend on the function of endothelial cells and fibrin formation. Endothelial cells may also synthesize and excrete PA inhibitor (PAI) which inhibits immediately, PA once released. The rates of synthesis and excretion of PA and PAI by endothelial cells are regulated by various factors. Among them, thrombin stimulates the release of PA whereas activated protein C may decrease the release of PAI. Thus, both enzymes enhance fibrinolytic potential. PA which has escaped from inhibition by PAI binds to fibrin. 2-Plasmin inhibitor ( 2PI) inhibits the binding of plasminogen to fibrin, thereby suppressing this fibrin-associated plasminogen activation. A part of 2PI is cross-linked to fibrin by activated factor XIII when fibrin is formed, and the 2PI thus cross-linked to fibrin inhibits in situ plasmin formed on fibrin. Thus, 2PI as well as PAI plays a central role in inhibition of fibrinolysis. |
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Keywords: | thrombi plasminogen activator plasmin /content/r7184h363857200r/xxlarge945.gif" alt=" agr" align=" BASELINE" BORDER=" 0" >2Plasmin inhibitor factor XIII fibrinolysis |
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