Flow pulsatility is a critical determinant of oxidative stress in endothelial cells

Atherosclerotic plaques are found in regions exposed to disturbed flow, sug gesting the active participation of the hemodynamic environment in atheroge nesis. Indeed, unidirectional and oscillatory flow patterns (ic, bidirectio nal) have been shown to induce contrasting effects on endothelial function. The put-pose of the present study was to evaluate the effect of these 2 fl ow patterns characterizing plaque-free and plaque-prone regions, respective ly, on the oxidative stress of endothelial cells. NADH-dependent oxidase ac tivity was shown to be equally induced (2- to 3-fold) in endothelial cells exposed to pulsatile unidirectional or oscillatory flow patterns. Under the se flow conditions, an increase in endothelial cell oxidative state compare d with static cultures was observed. Pulsatility of flow, but not cyclic st retch, was a critical determinant of flow-induced superoxide anion producti on. P22phox mRNA level increased in cells exposed to both unidirectional an d oscillatory shear stress, suggesting that p22phox gene expression upregul ation contributes to flow-induced increase in superoxide anion production i n endothelial cells. In conclusion, we demonstrate a flow-induced increase in oxidative stress in endothelial cells. This chronic increase is dependen t on the pulsatile nature of flow and is mediated in part by upregulation o f an NADH-dependent oxidase expression.