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 inhi bitor of both tissue-type and urokinase-type plasminogen activators (t PA and uPA, respectively) and may be the primary regulator of plasmino gen activation in vivo. A primary hypothesis of the author's work is t hat the expression of PAI-1 in vivo is not only precisely regulated, b ut also that the inappropriate expression of this potent inhibitor may suppress the normal fibrinolytic system of the tissues and create a l ocal prothrombotic state. This condition may result in pathological fi brin deposition following injury and/or tissue factor expression. The recent demonstration that PAI-1 mRNA levels are elevated in atheroscle rotic human arteries and in tissues of the endotoxic mouse is consiste nt with this possibility. These studies are reviewed.