[Molecular interactions during fibrinolysis. Search for new plasminogen activators]

The data on the kinetics of plasminogen activation by its tissue and urokinase-type plasminogen activators are reviewed. The mechanisms of this interaction in the presence of fibrin are analyzed. The regulatory role of fibrin in plasminogen activation involving its direct interaction with tissue-type plasminogen activator and indirect interaction with urokinase-type plasminogen activator is demonstrated. The functions of these activators in fibrinolysis as well as clinical and experimental data demonstrating their mutual contribution to thrombus elimination were revealed. The criteria of thrombolytic efficacy of plasminogen activators were defined, and the data on fibrinolytic preparations obtained by chemical modification, recombinant DNA techniques, or their combination were analyzed from this standpoint. The prospects for the development of new-generation plasminogen activators and the importance of studying the properties of thrombolytic compositions were demonstrated. The results of molecular, physiological, and clinical studies concerning the therapy with plasminogen activators are considered.