Endothelial cells proteolytic activity

Fibrinolysis refers to the process of fibrin digestion by the fibrin-specific protease, plasmin. The fibrinolytic system is similar to the coagulation system in that the precursor form of the serine protease plasmin circulates in an inactive form as plasminogen. In response to injury, endothelial cells synthesize and release tissue plasminogen activator (t-PA), which converts plasminogen to plasmin (Figure 34-3). Plasmin remodels the thrombus and limits its extension by proteolytic digestion of fibrin. 

Protein C. This vitamin K-dependent glycoprotein serine protease zymogen is produced in the liver. It is an anticoagulant with species specificity (19—21). Protein C is activated to Protein Ca by thrombomodulin, a protein that resides on the surface of endothelial cells, plus thrombin in the presence of calcium. In its active form, Protein Ca selectively inactivates, by proteolytic degradation, Factors V, Va, VIII, and Villa. In this reaction the efficiency of Protein Ca is enhanced by complex formation with free Protein S. In addition, Protein Ca activates tissue plasminogen activator, which promotes the conversion of plasminogen [9001-91-6] to plasmin [9001-90-5]. 

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The intetaction of proteolytically-active a-tfarombin with platelets and other cells of the vasculature, such as endothelial cells and smooth muscle cells, plays a major role in both normal hemostasis and atherosclerosis. Despite extensive studies in numerous laboratories extending back over thirty years, major questions regarding the mechanism of these interactions remain uruesolved. Furthermore, since dirombin can also induce chemotaxis and adhesion of inflammatory cells, and fibroblast mitogenesis, the importance of elucidating the nature of its receptor, or receptors, extends r beyond its role in platelet activation. However, this review will be restricted mainly to considerations of thrombin receptors in human platelets. 

As a result of the contact of blood with none-ndothelial surfaces, several humoral and cellular systems can be activated. Exposure of blood proteins and cells to blood contacting medical devices can activate plasma proteolytic systems (coagulation (blood clotting system), fibrinolysis (process by which clot is broken down), complement cascade (a system of soluble proteins involved in microbiocidal activity and the release of inflammatory components), Kallekrein-kinin and contact systems) and at least three cellular elements (leukocytes, endothelial cells, and platelets). Contrary to the normal situations whereby these mechanisms are localized and intended to promote wound healing, activation of these systems by medical devices can result in nonlocalized systemic reactions. The preclinical and clinical assessments of hemocompatibility are designed to minimize modification of these systems. 

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