Beyond fibrinolysis: the role of plasminogen activator inhibitor-1 and vitronectin in vascular wound healing.

Plasminogen activator inhibitor-1 (PAI-1), as the name implies, is the primary in vivo inhibitor of both tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). PAI-1 also binds to other nonproteinase ligands, including the matrix protein vitronectin, glycosaminoglycans such as heparin, and the endocytic clearance receptor, the low-density-lipoprotein-receptor-related protein (LRP). PAI-1 belongs to the superfamily of serine proteinase inhibitors (serpins), and, like other serpins, it acts as "suicide inhibitor" that reacts only once with a target proteinase. The suicide mechanism results in irreversible modification of the serpin and an extensive change in its conformation. In the case of PAI-1, this conformational change is important not only for inhibition of the proteinase, but it also causes changes in affinity for vitronectin and LRP. These changes have important consequences for cell migration.