Agents which Increase Synthesis and Release of Tissue-Type Plasminogen Activator

The plasminogen/plasmin system represents a highly regulated enzyme cascade that generates localized proteolysis. The system plays a key role in an extraordinary number of normal biological and pathophysiological contexts such as fibrinolysis, cell migration, and tissue remodeling. Plasminogen, present in high concentrations in blood and other body fluids, constitutes an abundant source of latent proteolytic activity. Conversion of the inactive proenzyme plasminogen into the active serine proteinase plasmin is catalyzed by plasminogen activators. The two main physiological plasminogen activators are tissue-type and urokinase-type plasminogen activator (tPA and uPA, respectively). Consistent with the important role of the plasminogen/plasmin system in so many processes, the action of tPA and uPA is well controlled by specific interactions between the various components, the synthesis and/or release of tPA and uPA, and the presence of specific protease inhibitors.