The Biochemistry, Physiology and Pathological roles of PAI-1 and the requirements for PAI-1 inhibition in vivo.
Plasminogen activator inhibitor-1 (PAI-1) is the primary physiological inhibitor of both tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA) and is consequently one the most important inhibitors of the plasminogen/plasmin system. PAI-1 attenuates fibrinolysis and increased levels of active PAI-1 have been associated with an increased risk for cardiovascular diseases. PAI-1 knock-out mice as well as PAI-1 overexpressing mice have been generated and characterized to study the role of PAI-1 in vivo. A number of PAI-1 inhibitors have been generated to study the pharmacological effect of PAI-1 inhibition in vitro and in vivo. The current review provides an overview of 1) the biochemical features of PAI-1, 2) the role of PAI-1 in diverse pathologies, 3) the in vitro and in vivo data obtained with PAI-1 inhibitors and 4) the vitronectin, glycosylation and species dependency of PAI-1 inhibition.
Laboratory for Pharmaceutical Biology, Department of Pharmaceutical and Pharmacological Sciences, Katholieke Universiteit Leuven, Belgium.
Britt
B
Van De Craen
Paul J
PJ
Declerck
Ann
A
Gils
D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods; D005342:Fibrinolysis; D005786:Gene Expression Regulation; D006801:Humans; D008659:Metabolic Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019096:Vitronectin / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D019096:Vitronectin