TISSUE FACTOR GENE-EXPRESSION IN THE ADIPOSE TISSUES OF OBESE MICE

Altered expression of proteins of the fibrinolytic and coagulation cas cades in obesity may contribute to the cardiovascular risk associated with this condition. We previously reported that plasminogen activator inhibitor 1 (PAI-1) is dramatically up-regulated in the plasma and ad ipose tissues of genetically obese mice. This change may disturb norma l hemostatic balance and create a severe hypofibrinolytic state. Here we show that tissue factor (TF) gene expression also is significantly elevated in the epididymal and subcutaneous fat pads from ob/ob mice c ompared with their lean counterparts, and that its level of expression in obese mice increases with age and the degree of obesity. Cell frac tionation and in situ hybridization analysis of adipose tissues indica te that TF mRNA is increased in adipocytes and in unidentified stromal vascular cells. Transforming growth factor beta (TGF-beta) is known t o be elevated in the adipose tissue of obese mice, and administration of TGF-beta increased TF mRNA expression in adipocytes in vivo and in vitro. These observations raise the possibility that TF and TGF-beta m ay contribute to the increased cardiovascular disease that accompanies obesity and related non insulin-dependent diabetes mellitus, and that the adipocyte plays a key role in this process. The recent demonstrat ion that TF also influences angiogenesis, cell adhesion, and signaling suggests that its exact role in adipose tissue physiology/pathology, may be complex.