Shear stress preconditioning modulates endothelial susceptibility to circulating TNF-α and monocytic cell recruitment in a simplified model of arterial bifurcations
Shear stress preconditioning modulates endothelial susceptibility to circulating TNF-α and monocytic cell recruitment in a simplified model of arterial bifurcations
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DOI：
10.1016/j.atherosclerosis.2009.04.034
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发表时间：
2009-11-01
期刊：
影响因子：
5.3
通讯作者：
Garlichs, Christoph D.
中科院分区：
文献类型：
--
作者：
Cicha, Iwona;Beronov, Kamen;Garlichs, Christoph D.
目的：动脉粥样硬化斑块的形成是局部剪切应力模式和炎症过程共同作用的结果。本研究在动脉分叉的简化模型中研究了内皮对剪切应力与炎性细胞因子 TNF-α 的结合的反应。方法：将人脐静脉内皮细胞 (EC) 在分叉流通玻片中暴露于层流或不均匀的剪切应力，然后用 TNF-α 刺激。为了研究细胞粘附，用含有 THP-1 单核细胞的培养基灌注 EC。通过免疫荧光测定内皮蛋白表达。结果：单核细胞与未刺激的EC的粘附在层流剪切应力下几乎检测不到，并且在非均匀剪切应力下略有增加。将 EC 暴露于不均匀剪切应力并结合 TNF-α，可诱导单核细胞募集增加 12 倍，并显着诱导内皮 E-选择素和 VCAM-1 表达。在暴露于层流剪切应力的 EC 中，这两种效应都被阻止了。在没有剪切应力预处理的情况下，层流和非均匀剪切应力区域之间 TNF-α 诱导的单核细胞募集和粘附分子表达的显着差异被消除。辛伐他汀 (1 mu mol/L) 通过抑制 VCAM-1 表达，将非均匀剪切应力和 TNF-α 诱导的单核细胞粘附增加抑制约 30%。红酒活性成分白藜芦醇在 20 μmol/L 浓度下可抑制 VCAM-1 和 E-选择素的表达，并使单核细胞的募集减少 50%。结论：非均匀剪切应力诱导内皮细胞对循环 TNF-α 的敏感性和单核细胞的粘附。干扰这一过程可能会抑制动脉粥样硬化易发区域的炎症反应。 (C) 2009 Elsevier Ireland Ltd. 保留所有权利。
Objective: Atherosclerotic plaque formation results from a combination of local shear stress patterns and inflammatory processes. This study investigated the endothelial response to shear stress in combination with the inflammatory cytokine TNF-alpha in a simplified model of arterial bifurcation.Methods: Human umbilical vein endothelial cells (ECs) were exposed to laminar or non-uniform shear stress in bifurcating flow-through slides, followed by stimulation with TNF-alpha. To study cell adhesion, ECs were perfused with medium containing THP-1 monocytic cells. Endothelial protein expression was determined by immunofluorescence.Results: Adhesion of monocytic cells to unstimulated ECs was nearly undetectable under laminar shear stress and was slightly increased under non-uniform shear stress. Exposure of ECs to non-uniform shear stress in combination with TNF-alpha induced a 12-fold increase in monocytic cell recruitment and a significant induction of endothelial E-selectin and VCAM-1 expression. Both these effects were prevented in ECs exposed to laminar shear stress. The significant differences in TNF-alpha-induced monocytic cell recruitment and adhesion molecule expression between laminar and non-uniform shear stress regions were abolished in the absence of shear stress preconditioning. Simvastatin (1 mu mol/L) suppressed the non-uniform shear stress-and TNF-alpha-induced increase in monocytic cell adhesion by about 30% via inhibition of VCAM-1 expression. Resveratrol, the active component of red wine, inhibited the expression of both VCAM-1 and E-selectin, and reduced monocytic cell recruitment by 50% at 20 mu mol/L.Conclusions: Non-uniform shear stress induces endothelial susceptibility to circulating TNF-alpha and adhesion of monocytic cells. Interference with this process may inhibit inflammatory response in atherosclerosis-prone regions. (C) 2009 Elsevier Ireland Ltd. All rights reserved.