Fluid shear stress attenuates tumor necrosis factor-α-induced tissue factor expression in cultured human endothelial cells

Yutaka Matsumoto, Yohko Kawai, Kiyoaki Watanabe, Kazuo Sakai, Mitsuru Murata, Makoto Handa, Shin Nakamura, Yasuo Ikeda

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32 Citations (Scopus)

Abstract

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)-α-induced tissue factor (TF) expression in cultured human umbilical vein endothelial calls (HUVECs), using a modified cone-plate viscometer. Shear stresses at physiological levels reduced TNF-α (100 U/mL)- induced TF expression at both mRNA end 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-α 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.

Original languageEnglish
Pages (from-to)4164-4172
Number of pages9
JournalBlood
Volume91
Issue number11
Publication statusPublished - 1998 Jun 1

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Matsumoto, Y., Kawai, Y., Watanabe, K., Sakai, K., Murata, M., Handa, M., Nakamura, S., & Ikeda, Y. (1998). Fluid shear stress attenuates tumor necrosis factor-α-induced tissue factor expression in cultured human endothelial cells. Blood, 91(11), 4164-4172.