The structural basis for the pathophysiological relevance of PAI-I in cardiovascular diseases and the development of potential PAI-I inhibitors.
Plasminogen activator inhibitor-I (PAI-I) is an important component of the plasminogen/plasmin system as it is the main inhibitor of tissue-type and urokinase-type plasminogen activator. Consequently, PAI-I plays an important role in cardiovascular diseases (mainly through inhibition of t-PA), and in cell migration and tumor development (mainly through inhibition of u-PA and interaction with vitronectin). As a member of the serpin superfamily, PAI-I shares important structural properties with other serpins. However, PAI-I also exhibits unique conformational and functional properties. The current review provides an overview of the knowledge on PAI-I gathered since its discovery two decades ago. We discuss (a) its structural properties of the protein and their subsequent relation to functional activities, (b) its role in a wide variety of (patho)physiological processes and (c) a number of strategies to interfere with its functional properties eventually aiming at pharmacological modulation of this risk factor.
Laboratory for Pharmaceutical Biology and Phytopharmacology, Katholieke Universiteit Leuven, E. Van Evenstraat 4, B-3000 Leuven, Belgium.
Ann
A
Gils
Paul J
PJ
Declerck
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001665:Binding Sites; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D002465:Cell Movement; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D009369:Neoplasms / Q000473:pathology; D010455:Peptides / Q000737:chemistry; D017395:Plasminogen Activator Inhibitor 1 / Q000502:physiology*; D015849:Plasminogen Inactivators / Q000627:therapeutic use*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry
D000911:Antibodies, Monoclonal; D010455:Peptides; D017395:Plasminogen Activator Inhibitor 1; D015849:Plasminogen Inactivators; D011994:Recombinant Proteins