© 1999 American Heart Association, Inc.
Original Contributions |
Resveratrol, a Polyphenolic Compound Found in Wine, Inhibits Tissue Factor Expression in Vascular Cells
A Possible Mechanism for the Cardiovascular Benefits Associated With Moderate Consumption of Wine
From the Departments of Molecular Biology and Biochemistry, The University of Texas Health Center at Tyler.
Correspondence to Usha R. Pendurthi, PhD, Department of Molecular Biology, The University of Texas Health Center at Tyler, 11937 US Highway 271, Tyler, TX 75708. E-mail usha{at}uthct.edu
Abstract—A number of studies
suggest that moderate consumption of red wine may be more effective
than other alcoholic beverages in decreasing the risk of
coronary heart disease mortality. The phytochemical resveratrol
found in wine, derived from grapes, has been thought to be responsible
for cardiovascular benefits associated with wine
consumption because it was shown to have antioxidant and
antiplatelet activities. In the present investigation, we
examined the effect of resveratrol on induction of tissue factor (TF)
expression in vascular cells that were exposed to
pathophysiological stimuli. The data
presented herein show that resveratrol, in a dose-dependent
manner, inhibited the expression of TF in endothelial
cells stimulated with a variety of agonists, including interleukin-1ß
(IL-1ß), tumor necrosis factor-
(TNF) and
lipopolysaccharide (LPS). A similar inhibition of TF induction
was also seen in LPS stimulated monocytes that were pretreated with
resveratrol before their stimulation with LPS. In addition, resveratrol
was shown to inhibit the LPS-induced expression of TNF mRNA in
endothelial cells and of TNF and IL-1ß mRNA in
monocytes. Nuclear run-on analysis in
endothelial cells showed that resveratrol inhibited TF
expression at the level of transcription. However, resveratrol did not
significantly alter the binding of the transcription factors
c-Fos/c-Jun and c-Rel/p65, the transcription factors required for the
induction of TF promoter in both endothelial cells and
monocytes. Similarly, resveratrol had no significant effect on the
binding of NF-
B in endothelial cells stimulated with
IL-1ß, TNF, and LPS. Overall, our data show that resveratrol could
effectively suppress the aberrant expression of TF and
cytokines in vascular cells, but it requires further
investigation to understand how resveratrol exerts its inhibitory
effect.
Key Words: tissue factor • resveratrol • endothelial cell • monocytes • cardioprotective effect
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