Flow pulsatility is a critical determinant of oxidative stress in endothelial cells.
Atherosclerotic plaques are found in regions exposed to disturbed flow, suggesting the active participation of the hemodynamic environment in atherogenesis. Indeed, unidirectional and oscillatory flow patterns (ie, bidirectional) have been shown to induce contrasting effects on endothelial function. The purpose of the present study was to evaluate the effect of these 2 flow patterns characterizing plaque-free and plaque-prone regions, respectively, on the oxidative stress of endothelial cells. NADH-dependent oxidase activity was shown to be equally induced (2- to 3-fold) in endothelial cells exposed to pulsatile unidirectional or oscillatory flow patterns. Under these flow conditions, an increase in endothelial cell oxidative state compared with static cultures was observed. Pulsatility of flow, but not cyclic stretch, was a critical determinant of flow-induced superoxide anion production. P22phox mRNA level increased in cells exposed to both unidirectional and oscillatory shear stress, suggesting that p22phox gene expression upregulation contributes to flow-induced increase in superoxide anion production in endothelial cells. In conclusion, we demonstrate a flow-induced increase in oxidative stress in endothelial cells. This chronic increase is dependent on the pulsatile nature of flow and is mediated in part by upregulation of an NADH-dependent oxidase expression.
Silacci
P
P
Division of Hypertension and Vascular Medicine, CHUV, Lausanne, Switzerland. Paolo.Silacci@chuv.hospvd.ch
Desgeorges
A
A
Mazzolai
L
L
Chambaz
C
C
Hayoz
D
D
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001161:Arteriosclerosis / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D026901:Membrane Transport Proteins; D009252:NADPH Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D019255:NADPH Oxidases; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D013314:Stress, Mechanical; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000975:Antioxidants; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D013481:Superoxides; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase; D000111:Acetylcysteine