Fat cell function and fibrinolysis

Plasminogen activator inhibitor-1 (PAI-1) is a specific inhibitor of plasmi nogen activators and may be the principal regulator of plasminogen activati on in vivo. PAI-1 levels are elevated in insulin-resistant subjects and are associated with an increased risk of atherothrombosis, After adjustment fo r metabolic parameters, increased PAI-1 levels were no longer considered as a cardiovascular risk factor. The mechanisms underlying the strong associa tion between PAI-1 levels and the metabolic disturbances found in insulin r esistance are still not understood. Several studies have suggested that vis ceral adipose tissue may be a major source of PAI-1. Accordingly, adipose t issue PAI-1 production particularly that from visceral fat, was found to be elevated in obese human subjects. Within human adipose tissue, stromal cel ls appear to be the main cells involved in PAI-1 synthesis. This review dis cusses the potential mechanisms linking adipose tissue to plasma PAI-1 leve ls such as the intervention of cytokines (TNF alpha and TGF beta), free fat ty acids and hormones (insulin and glucocorticoids). Moreover alteration of adipose tissue cellular composition induced by the modulation of PAI-1 exp ression opens a novel field of interest.