Effect of plasminogen activator inhibitor-1 in diabetes mellitus and cardiovascular disease

Am J Med. 2003 Dec 8;115 Suppl 8A:62S-68S. doi: 10.1016/j.amjmed.2003.08.014.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Clinical Trials as Topic
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / physiopathology
  • Humans
  • Insulin Resistance / physiology
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Plasminogen Activator Inhibitor 1 / therapeutic use*
  • Renin-Angiotensin System / drug effects
  • Ventricular Remodeling / drug effects

Substances

  • Plasminogen Activator Inhibitor 1