Neutrophil Adhesion on Endothelial Cells in a Novel Asymmetric Stenosis Model: Effect of Wall Shear Stress Gradients
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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 nonstimulated ECs for 1 or 6 h at 1.25 or 6.25 dynes/cm2 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.
KeywordsIn vitro perfusion Wall shear stress Coronary plaque Inflammation Vulnerability Stability
We thank L. Danielczak and K. Markey for their technical assistance in the experiments.
This work was supported by grants from the Canadian Foundation for Innovation (CFI), the National Sciences and Engineering Research Council (NSERC), the Canadian Institutes of Health Research (CIHR), the Fonds Québécois de la Recherche sur la Nature et les Technologies (FQRNT), and the Eugenie Ulmer Lamothe Fund (EUL).
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