EFFECTS OF WALL SHEAR-STRESS AND FLUID RECIRCULATION ON THE LOCALIZATION OF CIRCULATING MONOCYTES IN A 3-DIMENSIONAL FLOW MODEL

There is a correlation between the location of early atherosclerotic l esions and the hemodynamic characteristics at those sites. Circulating monocytes are key cells in the pathogenesis of atherosclerotic plaque s and localize at sites of atherogenesis. The hypothesis that the dist ribution of monocyte adhesion to the vascular wall is determined in pa rt by hemodynamic factors was addressed by studying monocyte adhesion in an in vitro how model in the absence of any biological activity in the model wall. Suspensions of U937 cells were perfused (Re = 200) thr ough an axisymmetric silicone flow model with a stenosis followed by a reverse step. The model provided spatially varying wall shear stress, flow separation and reattachment, and a three-dimensional flow patter n. The cell rolling velocity and adhesion rates were determined by ana lysis of videomicrographs. Wall shear stress was obtained by numerical solution of the equations of fluid motion. Cell adhesion patterns wer e also studied in the presence of chemotactic peptide gradients. The c ell rolling velocity varied linearly with wall shear stress. The adhes ion rate tended to decrease with increasing local wall shear stress, b ut was also affected by the radial component of velocity and the dynam ics of the recirculation region and flow reattachment. Adhesion was in creased in the vicinity of chemotactic peptide sources downstream of t he expansion site. Results with human monocytes were qualitatively sim ilar to the U937 experiments. Differences in the adhesion rates of U93 7 cells occurring solely as a function of the fluid dynamic properties of the how field were clearly demonstrated in the absence of any biol ogical activity in the model wall.