Nutritional influences on the fibrinolytic system.

Fibrinolytic system In addition to the mechanisms which achieve haemostasis by the formation of fibrin-stabilized platelet plugs, man possesses an efficient system designed to remove unwanted or excessive fibrin. The enzyme which cleaves fibrin into soluble degradation products is termed plasmin (EC 3.4.4.14); it is present in the circulation as a zymogen known as plasminogen. The activation of plasminogen to plasmin is achieved by agents termed plasminogen activators. The major activators of blood and tissues are of two types which differ in structure and properties. They are termed urokinase-type activator and tissue-type activator: only the latter has a high affinity for fibrin. Vascular endothelial cells contain tissue-type activator and this can be released into the circulation by such stimuli as exercise, venous occlusion and vasoactive agents. Blood also contains inhibitors of the fibrinolytic system which can neutralize the activity of either formed plasmin or plasminogen activator. The principal inhibitor of plasmin is a 70000 dalton glycoprotein termed a,-antiplasmin, and there is accumulating evidence for the existence of a specific inhibitor of plasminogen activator distinct from the known plasma protease inhibitors. A number of hypotheses on the mechanism of fibrinolysis has been advanced over the past two decades, but it is now generally agreed that circulating plasminogen is adsorbed onto fibrin, the interaction being mediated through lysine-binding sites on the plasminogen molecule (Wiman & Collen, 1978). Tissue-type activator is also bound to fibrin and in this situation its activating properties are markedly enhanced. It is likely that fibrinolysis takes place through the activation of fibrin-bound plasminogen by fibrin-bound activator leading to the localized formstion of plasmin and the consequent degradation of the fibrin. Any free plasmin released into the plasma is rapidly inactivated by a,-antiplasmin, preventing destruction of fibrinogen and other susceptible proteins. The importance of the physiological role of the fibrinolytic system in the prevention of fibrin deposition and persistence may be deduced from the thrombotic tendency in families with a hereditary defect in the plasminogen molecule leading to impaired plasmin activity on activation (Aoki, 1984) and, more strikingly, in the families with impaired release of plasminogen activator from the blood vessel wall (Johansson et al. 1978; Jargensen et at. 1982; Stead et al. 1983).