[Biochemical and physiologic principles of tissue-type plasminogen activator]

After wound healing the protective fibrin clot is removed by the fibrinolytic system. In addition fibrinolysis is one of the most important counter-reactions of blood coagulation. Fibrinolysis is controlled by activation and inhibition processes. Tissue type plasminogen activator (t-PA) and Pro-urokinase (single chain urokinase; scu-PA) hold a key position in physiological plasminogen activation. Plasmin itself is a rather unspecific protease capable of degrading a great variety of proteins besides fibrin. In vivo however--except for certain pathological situations--the fibrinolytic process is restricted to its actual target the fibrin clot. This surprising situation in terms of structure function interrelation is physiologically managed by N-terminal modules in the protein structure of the essential factors providing fibrin affinity. Free plasmin will be immediately inactivated by alpha 2-antiplasmin. Therefore fibrin plays a central role as cofactor in the fibrinolytic system in determining initiation and localization of the fibrinolytic process. Because of the superior properties of t-PA and scu-PA with respect to fibrin specificity both activators must be regarded as the future thrombolytic agents for therapy.