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.
Gils
Ann
A
Laboratory for Pharmaceutical Biology and Phytopharmacology, Katholieke Universiteit Leuven, E. Van Evenstraat 4, B-3000 Leuven, Belgium.
Declerck
Paul J
PJ
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