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 vitronect in, glycosaminoglycans such as heparin, and the endocytic clearance re ceptor, the low-density-lipoprotein-receptor-related protein (LRP). PA I-1 belongs to the superfamily of serine proteinase inhibitors (serpin s), and, like other serpins, it acts as ''suicide inhibitor'' that rea cts only one with a target proteinase. The suicide mechanism results i n irreversible modification of the serpin and an extensive change in i ts conformation. In the case of PAI-1, this conformational change is i mportant not only for inhibition of the proteinase, but it also causes changes in affinity for vitronectin and LRP. These changes have impor tant consequences for cell migration. (C) 1998, Elsevier Science Inc.