Department of Cardiology and Angiology, University of Erlangen-Nuremberg, Erlangen, Germany.
Clin Hemorheol Microcirc. 2010;46(2-3):203-10. doi: 10.3233/CH-2010-1346.
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.
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.
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.
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.
动脉粥样硬化斑块在经受非均匀切应力的动脉区域形成，由白细胞-内皮细胞相互作用增加引发。在这项研究中，我们研究了不同切应力模式对单核细胞募集到内皮细胞的影响。
在分岔流动式载玻片上，将人脐静脉内皮细胞（EC）暴露于层流或非均匀切应力下，然后用 TNF-α 刺激 2 小时。为了研究细胞黏附，用含有 THP-1 单核细胞的培养基灌流 EC 1 小时。通过免疫荧光测定内皮蛋白表达。
暴露于非均匀切应力和 TNF-α导致黏附分子的渐进诱导，以及单核细胞黏附的增加，在 0.5-3 小时观察到。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 暴露于降低的剪切应力下，导致非均匀剪切应力区域中的梯度陡度降低。将剪切应力从 10 降低到 5 和 2 达因/平方厘米导致在层流剪切应力下单核细胞黏附增加。然而，在这些条件下，非均匀剪切应力下黏附的单核细胞显著减少。此外，在暴露于与流动方向平行的剪切应力梯度的区域中，单核细胞黏附显著低于具有横向梯度的非均匀剪切应力区域。
暴露于非均匀切应力导致黏附分子的渐进诱导，并响应循环 TNF-α募集单核细胞。分叉处增强的单核细胞募集不仅受剪切应力梯度的幅度和陡度影响，还受其与流动方向的关系影响。
