REGULATION OF THE THROMBOLYTIC POTENTIAL OF THE VASCULAR WALL BY PLASMINOGEN-ACTIVATOR INHIBITOR-1 (PAI-1)

Plasminogen activator inhibitor-1 (PAI-1) is a rapid and specific inhibitor of both tissue-type and urokinase-type plasminogen activators (tPA and uPA, respectively) and may be the primary regulator of plasminogen activation in vivo. A primary hypothesis of the author's work is that the expression of PAI-1 in vivo is not only precisely regulated, but also that the inappropriate expression of this potent inhibitor may suppress the normal fibrinolytic system of the tissues and create a local prothrombotic state. This condition may result in pathological fibrin deposition following injury and/or tissue factor expression. The recent demonstration that PAI-1 mRNA levels are elevated in atherosclerotic human arteries and in tissues of the endotoxic mouse is consistent with this possibility. These studies are reviewed.