Neutrophil Adhesion on Endothelial Cells in a Novel Asymmetric Stenosis Model: Effect of Wall Shear Stress Gradients

摘要

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-α stimulated and non-stimulated ECs for 1 or 6 hrs at 1.25 or 6.25 dynes/cm² and compared to static conditions. Cytokine stimulation increased significantly endothelial cell 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 endothelial cells 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-endothelial cell interactions in the atherosclerotic process, especially in wall shear gradient regions. This is important clinically, potentially helping to explain plaque stability.