Fat cell function and fibrinolysis.
Plasminogen activator inhibitor-1 (PAI-1) is a specific inhibitor of plasminogen activators and may be the principal regulator of plasminogen activation in vivo. PAI-1 levels are elevated in insulin-resistant subjects and are associated with an increased risk of atherothrombosis. After adjustment for metabolic parameters, increased PAI-1 levels were no longer considered as a cardiovascular risk factor. The mechanisms underlying the strong association between PAI-1 levels and the metabolic disturbances found in insulin resistance are still not understood. Several studies have suggested that visceral adipose tissue may be a major source of PAl-1. Accordingly, adipose tissue PAI-1 production particularly that from visceral fat, was found to be elevated in obese human subjects. Within human adipose tissue, stromal cells appear to be the main cells involved in PAI-1 synthesis. This review discusses the potential mechanisms linking adipose tissue to plasma PAI-1 levels such as the intervention of cytokines (TNFalpha and TGFbeta), free fatty acids and hormones (insulin and glucocorticoids). Moreover alteration of adipose tissue cellular composition induced by the modulation of PAI-1 expression opens a novel field of interest.
Laboratory of Hematology, Faculty of Medicine, CHU Timone, Marseille, France.
M C
MC
Alessi
P
P
Morange
I
I
Juhan-Vague
D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D002318:Cardiovascular Diseases; D005230:Fatty Acids, Nonesterified / Q000502:physiology; D005342:Fibrinolysis; D005938:Glucocorticoids / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance; D009765:Obesity / Q000503:physiopathology; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000097:blood; D012307:Risk Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D016212:Transforming Growth Factor beta / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D005230:Fatty Acids, Nonesterified; D005938:Glucocorticoids; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D010959:Tissue Plasminogen Activator