Regulation of tissue factor gene expression in obesity

Altered expression of proteins of the fibrinolytic and coagulation cascades in obesity may contribute to the cardiovascular risk associated with this condition. In spite of this, the zymogenic nature of some of the molecules and the. presence of variable amounts of activators, inhibitors, and cofact ors. that alter their activity have made it difficult to accurately monitor changes in the activities of these proteins in tissues where they are synt hesized. Thus, as a first approach to determine whether tissue factor (TF) expression is altered in obesity, this study examined changes in TF mRNA in various tissues from lean and obese (ob/ob and db/db) mice. TF gene expres sion was elevated in the brain, lung, kidney, heart, liver, and adipose tis sues of both ob/ob and db/db mice compared with their lean counterparts. In situ hybridization analysis indicated that TF mRNA was elevated in bronchi al epithelial cells in the lung, in myocytes in the heart, and in adventiti al cells lining the arteries Including the aortic wall. Obesity is associat ed with insulin resistance and hyperinsulinemia, and administration of insu lin to lean mice induced TF mRNA in the kidney, brain, lung, and adipose ti ssue. These observations suggest that the hyperinsulinemia associated with insulin-resistant states, such as obesity, and noninsulin-dependent diabete s mellitus, may induce local TF gene expression in multiple tissues. The el evated TF, may contribute to the increased risk of atherothrombotic disease that accompanies these conditions. (Blood. 2001;98:3353-3358) (C) 2001 by The American Society of Hematology.