Basic Concepts of Fibrinolysis

A type I transmembrane protein called endothelial cell protein C receptor (EPCR), which is expressed at high levels exclusively on a subset of endothelial cells, has also been identified. EPCR has a role in the protein C pathway (30). EPCR binds to both protein C and activated protein C (APC) with equal affinity. Activation of protein C presumably requires interaction of the protein C-EPCR complex with the thrombin-thrombomodulin complex. APC that is formed as a result of this interaction is reversibly bound to EPCR until it dissociates to react subsequently with protein S. The APC-protein S complex inactivates activated factor V (Va). 

Although the fibrinolytic pathway is activated when thrombin binds to thrombomodulin, the thrombin-thrombomodulin complex, in addition to activating protein C (APC), activates a fibrinolysis inhibitor called the thrombin-activatable fibrinolysis inhibitor (TAFIa). Thus plasmin generation and, in turn, fibrinolysis are 

The lysine binding sites on free Lys-plasminogen or free Lys-plasmin are susceptible to inhibition by a2 plasmin, the primary inhibitor of plasmin, because these sites are not protected by interaction with fibrin. However, when Lys-plasminogen is tightly bound to the fragment E domain, it is rapidly activated by the 

The 68-kDa t-PA molecule, although synthesized as a single chain, undergoes modification to result in A and B polypeptide chains connected by a single disulfide bridge (36). This modification is mediated by factor Xa, tissue kallikrein, and directly on the surface of a thrombus by plasmin (37). The affinity of the A chain 

The fibrinolytic activity of scu-PA is more efficient than that of either LMW-UK or HMW-UK. Apparently, fibrin within a clot neutralizes an inhibitor in plasma that normally hinders binding of scu-PA to plasminogen, thereby facilitating binding of scu-PA to Glu-plasminogen and its resultant activation (37, 38). A cell surface receptor for scu-PA has been implicated in the activation of plasminogen and the internalization and degradation of u-PA complexed to inhibitors (39). 

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