Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, Georgia, USA.
Am J Physiol Heart Circ Physiol. 2010 Feb;298(2):H367-74. doi: 10.1152/ajpheart.00565.2009. Epub 2009 Nov 13.
To simulate the effects of shear stress in regions of the vasculature prone to developing atherosclerosis, we subjected human umbilical vein endothelial cells to reversing shear stress to mimic the hemodynamic conditions at the wall of the carotid sinus, a site of complex, reversing blood flow and commonly observed atherosclerosis. We compared the effects of reversing shear stress (time-average: 1 dyn/cm(2), maximum: +11 dyn/cm(2), minimum: -11 dyn/cm(2), 1 Hz), arterial steady shear stress (15 dyn/cm(2)), and low steady shear stress (1 dyn/cm(2)) on gene expression, cell proliferation, and monocyte adhesiveness. Microarray analysis revealed that most differentially expressed genes were similarly regulated by all three shear stress regimens compared with static culture. Comparisons of the three shear stress regimens to each other identified 138 genes regulated by low average shear stress and 22 genes regulated by fluid reversal. Low average shear stress induced increased cell proliferation compared with high shear stress. Only reversing shear stress exposure induced monocyte adhesion. The adhesion of monocytes was partially inhibited by the incubation of endothelial cells with ICAM-1 blocking antibody. Increased heparan sulfate proteoglycan expression was observed on the surface of cells exposed to reversing shear stress. Heparinase III treatment significantly reduced monocyte adhesion. Our results suggest that low steady shear stress is the major impetus for differential gene expression and cell proliferation, whereas reversing flow regulates monocyte adhesion.
为了模拟血管中易于发生动脉粥样硬化的区域的切应力效应，我们将人脐静脉内皮细胞置于反向切应力下，以模拟颈动脉窦壁处的血液动力学条件，颈动脉窦是血流复杂、反向且常见动脉粥样硬化的部位。我们比较了反向切应力（时均：1 dyn/cm(2)，最大：+11 dyn/cm(2)，最小：-11 dyn/cm(2)，1 Hz）、动脉稳态切应力（15 dyn/cm(2)）和低稳态切应力（1 dyn/cm(2)）对基因表达、细胞增殖和单核细胞黏附的影响。微阵列分析显示，与静态培养相比，大多数差异表达基因在这三种切应力方案下的调控方式相似。将这三种切应力方案相互比较，发现低平均切应力调节了 138 个基因，而流体反向切应力调节了 22 个基因。低平均切应力诱导的细胞增殖高于高切应力。只有暴露于反向切应力时才会诱导单核细胞黏附。单核细胞的黏附可部分被内皮细胞与 ICAM-1 阻断抗体孵育所抑制。在暴露于反向切应力的细胞表面观察到肝素硫酸蛋白聚糖表达增加。肝素酶 III 处理可显著降低单核细胞黏附。我们的结果表明，低稳态切应力是差异基因表达和细胞增殖的主要动力，而反向流动调节单核细胞黏附。
