Adaptive response of vascular endothelial cells to an acute increase in shear stress frequency

Abstract

Local shear stress sensed by arterial endothelial cells is occasionally altered by changes in global hemodynamic parameters, e.g., heart rate and blood flow rate, as a result of normal physiological events, such as exercise. In a recently study ( 41 ), we demonstrated that during the adaptive response to increased shear magnitude, porcine endothelial cells exhibited an unique phenotype featuring a transient increase in permeability and the upregulation of a set of anti-inflammatory and antioxidative genes. In the present study, we characterize the adaptive response of these cells to an increase in shear frequency, another important hemodynamic parameter with implications in atherogenesis. Endothelial cells were preconditioned by a basal-level sinusoidal shear stress of 15 ± 15 dyn/cm2 at 1 Hz, and the frequency was then elevated to 2 Hz. Endothelial permeability increased slowly after the frequency step-up, but the increase was relatively small. Using microarrays, we identified 37 genes that are sensitive to the frequency step-up. The acute increase in shear frequency upregulates a set of cell-cycle regulation and angiogenesis-related genes. The overall adaptive response to the increased frequency is distinctly different from that to a magnitude step-up. However, consistent with the previous study, our data support the notion that endothelial function during an adaptive response is different than that of fully adapted endothelial cells. Our studies may also provide insights into the beneficial effects of exercise on vascular health: transient increases in frequency may facilitate endothelial repair, whereas similar increases in shear magnitude may keep excessive inflammation and oxidative stress at bay.