Effects of Altered Plasminogen Activator Inhibitor-1 Expression on Cardiovascular Disease

Victoria      A. Ploplis

doi:10.2174/138945011797635803

Abstract

Plasminogen Activator Inhibitor-1 (PAI-1) is a multifunctional protein with the ability to not only regulate fibrinolysis through inhibition of plasminogen activation, but also cell signaling events which have direct downstream effects on cell function. Elevated plasma levels of this protein have been shown to have profound effects on the development and progression of cardiovascular diseases. However, results from a number of studies, especially those using PAI-1 deficient mouse models, have demonstrated that its function is ambiguous, with evidence of both preventing and enhancing various disease states. A number of lifestyle changes and pharmacological reagents have been identified that can regulate PAI-1 levels or function. Those reagents that target function are focused on its ability to regulate plasmin formation, and have been studied in in vivo models of thrombosis. Further investigations involving regulation of cell function could potentially resolve paradoxical issues associated with the function of this protein in regulating cardiovascular disease.

Keywords: Plasminogen activator inhibitor-1, gene knock out mice, cardiovascular disease, angiotensin converting enzyme inhibitor, myocardial infarction, atherosclerosis, cardiac fibrosis, DNAzyme, statin, proteases