title: PAI-1 antagonists: the promise and the peril.
abstract: The plasminogen activator (i.e., fibrinolytic) system is one of the key endogenous defense mechanisms against intravascular thrombosis. Thrombolytic agents represent the only direct way of augmenting fibrinolytic activity in humans, and have proven to be of value in the treatment of acute myocardial infarction and stroke. Although these agents are efficacious in the acute setting, they are not a viable option for long-term use. Net fibrinolytic activity is plasma is largely determined by the balance between tissue-type plasminogen activator (t-PA) and its natural, fast-acting inhibitor, plasminogen activator inhibitor-1 (PAI-1). The recent development of specific PAI-1 antagonists promises to expand the limits of understanding of the role of the fibrinolytic system in human disease, and to break through the current confines of therapeutic options that can effectively restore and augment the activity of the fibrinolytic system.
authors.affiliation: Northwestern University Feinberg School of Medicine, Department of Medicine, 201 E. Huron Street, Galter Pavilion, 3rd Floor, Suite 3-150, Chicago, Illinois 60611, USA. d-vaughan@northwestern.edu
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Vaughan
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005355:Fibrosis; D006801:Humans; D008297:Male; D009765:Obesity / Q000097:blood / Q000188:drug therapy; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1