The Effect of Spatial Shear Stress Gradient on Endothelial Elongation and eNOS Expression

Abstract

Objective As large spatial shear stress gradients are found in regions of the vasculature susceptible to atherosclerosis, this study examines the effect of such a gradient on flow-dependent endothelial cell behavior. Methods A flow chamber was designed that exposed porcine aortic endothelial cells to a nearly constant gradient over a physiologically relevant range of shear stress magnitude. The cells were analyzed with respect to elongation and protein expression level of endothelial nitric oxide synthase (eNOS). The latter, measured via quantitative immunofluorescence microscopy, was compared to eNOS expression by cells exposed to similar levels of shear stress in the absence of a gradient. Results Cell elongation increased with shear stress along the channel and was unaffected by gradient. Shear gradient suppressed the shear sensitivity of eNOS expression (p=0.002). Conclusion The protective role of shear stress, as manifested by increased eNOS expression, is diminished in the presence of a shear stress gradient, suggesting a role for this hemodynamic factor in atherosusceptibility. Supported by NIH grant H50442 and a Whitaker Foundation Graduate Research Fellowship.