Effect of a disturbed flow on adhesion of monocytes to a model of an arterial wall

Abstract

Monocytes are involved in the pathogenesis and localization of intimal hyperplasia and atherosclerosis in regions of disturbed flow in man. Hence, to investigate the mechanism of the localization of these vascular diseases, we created a state of disturbed flow distal to a 0.92 mm into 3.0 mm sudden tubular expansion consisting of a stainless steel upstream tube and a hybrid vascular graft by recirculating a cell culture medium through it in steady flow. Then by introducing fluorescence-labeled human blood monocytes (THP-1 cells) into the medium, we tested the effect of a disturbed flow (an annular vortex) on adhesion of monocytes to the endothelium of the hybrid graft. It was found that adhesion and invasion of THP-1 cells to the endothelium were the highest around the reattachment point (the toe of the annular vortex) where the flow was the slowest and wall shear stress was the lowest. They were the lowest at a location between the step of the tubular expansion and the reattachment point that was close to the vortex center where the flow was the fastest and wall shear stress was the highest. A similar distribution was also obtained with 20 nm diameter polystyrene microspheres used as a model of low-density lipoproteins (LDL). These results indicated that a disturbed flow itself provided favorable conditions for the adhesion of monocytes and LDL to the endothelium in regions of very slow flow, and hence low wall shear stress, by allowing them to make contact and interact with endothelial cells for a long time. This may explain, in part, why intimal hyperplasia and atherosclerotic lesions develop preferentially in regions of very slow flow.