Fluid shear stress attenuates tumor necrosis factor-α-induced tissue factor expression in cultured human endothelial cells
Fluid shear stress attenuates tumor necrosis factor-α-induced tissue factor expression in cultured human endothelial cells
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DOI：
10.1182/blood.v91.11.4164.411k29_4164_4172
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发表时间：
1998-06-01
期刊：
影响因子：
20.3
通讯作者：
Ikeda, Y
中科院分区：
文献类型：
--
作者：
Matsumoto, Y;Kawai, Y;Ikeda, Y
血流动力学在基因调控下调节各种内皮细胞功能。以前，我们已经表明，内皮细胞的纤溶活性增强的剪切力和细胞因子的协同作用。在这项研究中，我们研究了切应力对肿瘤坏死因子（TNF）-α诱导的组织因子（TF）在培养的人脐静脉内皮细胞（HUVECs）的表达的影响，使用改进的锥板粘度计。在生理水平的剪切应力降低TNF-α（100 U/mL）诱导的TF表达在mRNA和抗原水平，在剪切强度和剪切时间依赖性的方式，而剪切应力本身不诱导TF表达在HUVEC。在TNF-α刺激前15小时和刺激后6小时，以18达因/cm（2）的剪切力施加剪切力，通过使用抗TF单克隆抗体（HTF-K180）的流式细胞术测量的细胞表面上的表达也减少到三分之一。此外，TF的功能活性，如通过在FVIIa和Ca 2+存在下因子X的活化所评估的，也通过剪切应用而降低。然而，TF mRNA的稳定性并没有在剪切力的存在下降低。这些结果表明，剪切力作为一个重要的调节因子的表达在内皮细胞的转录水平。(C)1998年，美国血液学会。
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)-alpha-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-alpha (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. if 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/cm(2) for 15 hours before and 6 hours after TNF-alpha 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. (C) 1998 by The American Society of Hematology.