[PAI-1, the primary plasmatic inhibitor of fibrinolysis. Physiopathologic role and molecular mechanisms].
Plasminogen activator inhibitor 1 (PAI-1) is the primary physiological inhibitor of plasminogen activation in blood. PAI-1 is known to contribute to thrombus formation and to the development and the clinical course of acute and chronic cardiovascular diseases. Plasma levels of PAI-1 are regulated on a genetic basis but, more important, is the dependence on a series of other atherosclerotic risk factors like hypertriglyceridemia, diabetes and insulin resistance. The insulin resistance syndrome, which is characterized partly by obesity with visceral fat accumulation, is considered as a major regulator of PAI-1 expression. At least in vitro, insulin is a potent inducer of PAI-1 synthesis by human hepatic cells, and, we have recently disentangled the molecular mechanisms responsible for enhanced PAI-1 gene expression by insulin. However, clinical data fail to support a direct acute contribution of insulin in regulating circulating PAI-1 levels. Recently, it has been proposed that adipose tissue could be responsible for the elevated plasma PAI-1 level observed in insulin resistance. It now seems reasonable to view PAI-1 as one of the factors contributing to the complex gene-environment interactions involved in the formation and dissolution of thrombi.
Banfi
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C
Dipartimento di Scienze Farmacologiche, Università degli Studi, Milan, Italy.
Mussoni
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L
Tremoli
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E
D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics / Q000503:physiopathology; D048909:Diabetes Complications; D005342:Fibrinolysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D010958:Plasminogen / Q000502:physiology; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010960:Plasminogen Activators / Q000502:physiology; D012307:Risk Factors
D017395:Plasminogen Activator Inhibitor 1; D010958:Plasminogen; D010960:Plasminogen Activators