Effect of plasminogen activator inhibitor-1 in diabetes mellitus and cardiovascular disease.
Concentrations of plasminogen activator inhibitor-1 (PAI-1) are elevated beginning at the stage of impaired glucose tolerance and continuing through the development of diabetes mellitus and the metabolic syndrome. Evolving evidence of the central role of PAI-1 in mediating fibrosis and thrombosis increasingly supports the theory that it is a significant risk factor for macrovascular complications and cardiovascular disease, particularly in patients with diabetes. Several clinical studies have demonstrated a strong correlation between circulating PAI-1 levels and cardiovascular events and mortality. With the potentially severe effects of elevated PAI-1 levels becoming evident, there is increased interest in developing therapies targeted at reducing PAI-1 expression or circulating concentrations. Thus far, weight loss, inhibitors of the renin-angiotensin system, and insulin sensitization through use of thiazolidinediones (TZDs) appear to be the most promising strategies for managing elevated PAI-1 levels. Of these, TZD therapy is the only one that provides the benefits of both long-term glycemic control and improved cardiovascular risk profile. This article reviews the regulation of PAI-1, its activity in various disease states, and available treatment options.
Lyon
Christopher J
CJ
Division of Endocrinology, Diabetes and Hypertension, University of California at Los Angeles, Los Angeles, California 90095, USA.
Hsueh
Willa A
WA
D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002986:Clinical Trials as Topic; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
D017395:Plasminogen Activator Inhibitor 1