Department of Chemical Engineering, McGill University, Montreal, QC, Canada.
Ann Biomed Eng. 2010 Sep;38(9):2791-804. doi: 10.1007/s10439-010-0032-4. Epub 2010 Apr 13.
Leukocytes play a pivotal role in the progression of atherosclerosis. A novel three-dimensional in vitro asymmetric stenosis model was used to better investigate the role of local hemodynamics in the adhesion of leukocytes to an established plaque. The adhesion of a human promyelocytic cell line (NB4) on a human abdominal aortic endothelial cell (EC) monolayer was quantified. NB4 cells were circulated over TNF-alpha stimulated and nonstimulated ECs for 1 or 6 h at 1.25 or 6.25 dynes/cm(2) and compared to static conditions. Cytokine stimulation increased significantly EC expression of intercellular adhesion molecule and vascular cell adhesion molecule. Under static conditions, neutrophils adhered overall more than under flow, with decreased adhesion with increasing shear. Adhesion was significantly higher in the recirculation region distal to the stenosis than in the inlet. Preshearing the ECs decreased the expression of cell adhesion molecules in inflamed endothelium and significantly decreased adhesion. However, the ratio of adhesion between the recirculation zone and the inlet increased, hence exhibiting an increased regional difference. This work suggests an important role for neutrophil-EC interactions in the atherosclerotic process, especially in wall shear stress gradient regions. This is important clinically, potentially helping to explain plaque stability.
白细胞在动脉粥样硬化的进展中起着关键作用。一种新型的三维体外不对称狭窄模型被用来更好地研究局部血液动力学在白细胞黏附于已形成斑块中的作用。黏附作用是用人急性早幼粒细胞白血病细胞系（NB4）在人腹主动脉内皮细胞（EC）单层上进行定量检测的。在 1.25 或 6.25 达因/平方厘米和静态条件下，将 NB4 细胞循环流过 TNF-α 刺激和未刺激的 EC 1 或 6 小时。细胞因子刺激显著增加了 EC 细胞间黏附分子和血管细胞黏附分子的表达。在静态条件下，中性粒细胞的黏附总体上高于流动状态，随着剪切力的增加而减少。在狭窄部位远端的再循环区的黏附明显高于入口。预先剪切 EC 可降低炎症内皮细胞中细胞黏附分子的表达，并显著减少黏附。然而，再循环区和入口之间的黏附比率增加，因此表现出区域差异增加。这项工作表明，中性粒细胞-EC 相互作用在动脉粥样硬化过程中起着重要作用，特别是在壁切应力梯度区域。这在临床上很重要，可能有助于解释斑块稳定性。
