PRODUCTION OF PLASMINOGEN-ACTIVATOR INHIBITOR-1 BY HUMAN ADIPOSE-TISSUE - POSSIBLE LINK BETWEEN VISCERAL FAT ACCUMULATION AND VASCULAR-DISEASE

Plasminogen activator inhibitor type 1 (PAI-1) contributes to the path ogenesis of atherothrombosis. Its plasma level is strongly correlated with parameters that define the insulin resistance syndrome, in partic ular with BMI and visceral accumulation of body fat, suggesting that P AI-1 may be an adipose tissue-derived circulating peptide. The present study was designed to investigate PAI-1 expression by human adipose t issue and its different cellular fractions. Special interest has been paid to the amount of PAI-1 antigen produced by omental versus subcuta neous fat. PAI-1 protein detected by immunolocalization was present at the stromal and adipocyte levels. PAI-1 mRNA was detected in stromal vascular cells freshly isolated and under culture conditions. It was a lso detected in whole adipose tissue and adipocyte fraction under cult ure conditions. The mRNA signal from the adipocyte fraction was detect ed as early as 2 h of incubation. The increase in PAI-1 mRNA was follo wed by an increase in PAI-1 antigen in the conditioned medium that was suppressed by treatment with cycloheximide. Transforming growth facto r-beta 1 significantly increased PAI-1 antigen production by the adipo cyte fraction, whereas tumor necrosis factor-alpha did not have any ef fect. Interestingly, after 5 h of incubation, omental tissue explants produced significantly more PAI-1 antigen than did subcutaneous tissue from the same individual, whereas similar production of leptin by the two territories was observed. These results strongly suggest that hum an adipose tissue, in particular visceral tissue, can be an important contributor to the elevated plasma PAI-1 levels observed in central ob esity.