Influence of hemodynamic factors on the adhesion pattern of U937 cells in a flow model: Implications in atherosclerosis

Early atherosclerotic lesions are localized in regions of flow separation and relatively low wall shear stress. An early event in atherogenesis is adhesion of circulating monocytes to the arterial endothelium and transmigration into the vessel wall. The cell may then differentiate into a macrophage within the interstitium of the vessel wall. With ingestion of extracellular lipid, as is present in atheromata, the macrophage may develop into a foam cell. Presently, circulating monocytes are thought to be the main precursor of the foam cell, a characteristic cell of atherosclerotic lesions. The hypothesis tested is that the distribution of cell adhesion to the vascular wall is determined in large part by hemodynamics. In this study, the hemodynamic factors governing monocyte adhesion were examined by perfusing a suspension of activated U937 cells at Reynolds number 200 through an axisymmetric Sylgard model with a stenosis and a reverse step geometry. This geometry provided flow separation and recirculation as well as spatial variation in both wall shear stress and particle residence time. The rolling velocity of the cells and the distribution of adherent cells in both the presence and absence of chemoattractants was determined by image analysis of videomicrographs of the model surface. Wall shear stress values were obtained by computational methods.