Role of shear stress patterns in the TNF-α-induced atherogenic protein expression and monocytic cell adhesion to endothelium.
Role of shear stress patterns in the TNF-α-induced atherogenic protein expression and monocytic cell adhesion to endothelium.
复制标题
剪切应力模式在 TNF-α 诱导的致动脉粥样硬化蛋白表达和单核细胞与内皮粘附中的作用。
DOI：
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发表时间：
2010
影响因子：
2.1
通讯作者：
I. Cicha
中科院分区：
文献类型：
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作者：
K. Urschel;Anja Wörner;W. Daniel;C. Garlichs;I. Cicha
背景
动脉粥样硬化斑块在受到不均匀剪切应力的动脉区域发展，并由白细胞-内皮相互作用增加引发。在这项研究中，我们研究了不同的剪切力模式对单核细胞内皮募集的影响。
方法
将人脐静脉内皮细胞（EC）暴露于分叉流通载玻片中的层流或非均匀剪切应力，随后用TNF-α刺激2 h。为了研究细胞粘附，用含有THP-1单核细胞的培养基灌注EC 1小时。免疫荧光法检测内皮细胞蛋白表达。
结果
暴露于非均匀剪切应力和TNF-α导致粘附分子的进行性诱导，并在0.5-3 h内观察到单核细胞粘附增加。为了研究剪切应力模式在单核细胞募集中的相对作用，将EC暴露于降低水平的剪切应力，导致在非均匀剪切应力区域中梯度陡度降低。将剪切应力从10降低至5和2达因/cm 2导致在层流剪切应力下单核细胞粘附增加。然而，在这些条件下，非均匀剪切应力下的粘附单核细胞强烈减少。此外，在暴露于剪切应力梯度平行于流动方向的区域中，单核细胞粘附显著低于非均匀剪切应力区域，其特征在于横向梯度。
结论
暴露于非均匀剪切应力导致粘附分子的进行性诱导和单核细胞对循环TNF-α的应答募集。增强的单核细胞在分叉处的募集不仅受到剪切应力梯度的大小和陡度的影响，而且还受到其相对于流动的方向的影响。
BACKGROUND
Atherosclerotic plaques develop at arterial regions subjected to non-uniform shear stress, and are initiated by increased leukocyte-endothelial interactions. In this study, we investigated the effects of distinct shear stress patterns on endothelial recruitment of monocytic cells.
METHODS
Human umbilical vein endothelial cells (ECs) were exposed to laminar or non-uniform shear stress in bifurcating flow-through slides, followed by 2 h stimulation with TNF-α. To study cell adhesion, ECs were perfused with medium containing THP-1 monocytic cells for 1 h. Endothelial protein expression was determined by immunofluorescence.
RESULTS
Exposure to non-uniform shear stress and TNF-α lead to progressive induction of adhesion molecules and increase in monocytic cell adhesion observed over 0.5-3 h. To investigate the relative role of the shear stress patterns in monocytic cell recruitment, ECs were exposed to reduced levels of shear stress, resulting in a reduced gradient steepness in the non-uniform shear stress regions. Lowering the shear stress from 10 to 5 and 2 dyne/cm2 resulted in increased monocytic cell adhesion under laminar shear stress. However, in these conditions, adherent monocytic cells under non-uniform shear stress were strongly reduced. Moreover, in the region exposed to shear stress gradient parallel to flow direction, monocytic cell adhesion was significantly lower than in the region of non-uniform shear stress, characterized by transversal gradient.
CONCLUSION
Exposure to non-uniform shear stress results in progressive induction of adhesion molecules and monocytic cell recruitment in response to circulating TNF-α. Enhanced monocytic cell recruitment at bifurcations is affected not only by the magnitude and steepness of shear stress gradient, but also by its direction in relation to the flow.