Plasminogen activator inhibitor-1: physiologic role, regulation, and the influence of common pharmacologic agents.
Plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor of endogenous thrombolysis, thereby promoting thrombosis. PAI-1 is also a primary contributor to the development and recurrence of acute myocardial infarction. The renin angiotensin system, hypertriglyceridemia, hyperglycemia and hyperinsulinemia, and estrogen all influence the fibrinolytic system and PAI-1 in particular. Available data strongly suggest that angiotensin-converting enzyme (ACE) inhibitors and hormone replacement therapy with estrogen beneficially reduce PAI-1 production. Metformin, an agent commonly used for non-insulin-dependent diabetes mellitus (NIDDM), appears to favorably decrease PAI-1 production in NIDDM patients but not nondiabetic patients. Among the cholesterol-lowering statins, clinical literature evaluating pravastatin provides the most compelling data to support this agent's favorable effect on PAI-1. Other available statins either have not displayed an effect on PAI-1 or do not have clear data to conclusively define their effects on the fibrinolytic system.
Tsikouris
James P
JP
Texas Tech University, Health Sciences Center, School of Pharmacy, Lubbock 79430, USA.
Suarez
Jose A
JA
Meyerrose
Gary E
GE
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D002986:Clinical Trials as Topic; D003328:Coronary Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D015914:Estrogen Replacement Therapy; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006943:Hyperglycemia / Q000150:complications; D006946:Hyperinsulinism / Q000150:complications; D006949:Hyperlipidemias / Q000150:complications; D007004:Hypoglycemic Agents / Q000494:pharmacology; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D017395:Plasminogen Activator Inhibitor 1