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A Journal on Endocrine System Diseases
Indexed/Abstracted in: EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 1,118
Minerva Endocrinologica 2002 September;27(3):181-92
PAI-1, the primary plasmatic inhibitor of fibrinolysis. Physiopathologic role and molecular mechanisms
Banfi C., Mussoni L., Tremoli E.
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 disentagled 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-enviroment interactions involved in the formation and dissolution of thrombi.