ADIPOSE-TISSUE SECRETION OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 IN NONOBESE AND OBESE INDIVIDUALS

High plasma plasminogen activator inhibitor-1 (PAI-1) activity is a fr equent finding in obesity, and both PAI-1 and obesity are risk factors for cardiovascular disease. To study the mechanisms underlying increa sed PAI-1 levels in obese individuals, gene expression and secretion o f PAI-1 were measured in human abdominal subcutaneous adipose tissue. A total of 32 obese, otherwise healthy subjects and 10 never-obese hea lthy subjects with a body mass index (BMI) of 42.6 +/- 1.2 and 24.3 +/ - 1.9 kg/m(2) (mean +/- SEM), respectively, were investigated. Plasma PAI-1 activity, adipose tissue PAI-1 secretion and adipocyte PAI-1 mRN A levels were increased sevenfold (p < 0.0001), sixfold (p < 0.0001) a nd twofold (p < 0.05), respectively, in the obese group. There were cl ear associations between adipose tissue secretion of PAI-1 and PAI-1 m RNA levels on the one hand and fat cell volume on the other (r = 0.68, p < 0.0001 and r = 0.51, p < 0.01, respectively, in the obese group). PAI-1 mRNA levels were also related to the amount of PAI-1 secreted a mong obese individuals (r = 0.31, p = 0.09). It is concluded that adip ose tissue secretes significant amounts of PAI-1, that PAI-1 secretion from adipose tissue is increased in obesity, and that PAI-1 secretion is related to the lipid content and cell volume of fat cells. Plasma PAI-1 activity is elevated in obesity, at least in part due to increas ed gene expression in adipocytes, which, in turn, enhances PAI-1 secre tion from adipose tissue.