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Fluid Shear Stress Attenuates Tumor Necrosis Factor- -Induced
Tissue Factor Expression in Cultured Human Endothelial Cells
Yutaka Matsumoto,
Yohko Kawai,
Kiyoaki Watanabe,
Kazuo Sakai,
Mitsuru Murata,
Makoto Handa,
Shin Nakamura, and
Yasuo Ikeda
From the Departments of Internal Medicine, Laboratory Medicine, and
Blood Center, Keio University, School of Medicine, Tokyo; and the
Department of Cellular and Molecular Biology, Primate Research
Institute, Kyoto University, Aichi, Japan.
Hemodynamic forces modulate various endothelial cell functions under
gene regulation. Previously, we have shown that fibrinolytic activity
of endothelial cells is enhanced by the synergistic effects of shear
stress and cytokines. In this study, we investigated the effect of
shear stress on tumor necrosis factor (TNF)- -induced tissue factor
(TF) expression in cultured human umbilical vein endothelial cells
(HUVECs), using a modified cone-plate viscometer. Shear stresses at
physiological levels reduced TNF- (100 U/mL)-induced TF expression
at both mRNA and antigen levels, in a shear-intensity and exposure-time
dependent manner, whereas shear stress itself did not induce TF
expression in HUVECs. TF expressed on the cell surfaces measured by
flow cytometry using an anti-TF monoclonal antibody (HTF-K180) was also
decreased to one third by shear force applied at 18 dynes/cm2 for 15 hours before and 6 hours after TNF-
stimulation. Furthermore, functional activity of TF, as assessed by the
activation of factor X in the presence of FVIIa and Ca2+,
was also decreased by shear application. However, the stability of TF
mRNA was not decreased in the presence of shear stress. These results
suggest that shear force acts as an important regulator of TF
expression in endothelium at the transcriptional level.
Blood, Vol. 91 No. 11 (June 1), 1998:
pp. 4164-4172
© 1998 by The American Society of Hematology.

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