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Blood, 1 December 2001, Vol. 98, No. 12, pp. 3353-3358
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Regulation of tissue factor gene expression in obesity
Fahumiya Samad,
Manjula Pandey, and
David J. Loskutoff
From the Department of Vascular Biology, Scripps
Research Institute, La Jolla, CA.
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 cofactors that alter their activity have
made it difficult to accurately monitor changes in the activities of
these proteins in tissues where they are synthesized. 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 expression was
elevated in the brain, lung, kidney, heart, liver, and adipose tissues
of both ob/ob and db/db mice compared with their lean counterparts. In
situ hybridization analysis indicated that TF mRNA was elevated in
bronchial epithelial cells in the lung, in myocytes in the heart, and
in adventitial cells lining the arteries including the aortic wall.
Obesity is associated with insulin resistance and hyperinsulinemia, and
administration of insulin to lean mice induced TF mRNA in the kidney,
brain, lung, and adipose tissue. These observations suggest that the hyperinsulinemia associated with insulin-resistant states, such as
obesity and noninsulin-dependent diabetes mellitus, may induce local TF
gene expression in multiple tissues. The elevated TF may contribute to
the increased risk of atherothrombotic disease that accompanies these conditions.
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