Cyclic strain induces reactive oxygen species production via an endothelial NAD(P)H oxidase.
Vascular endothelial cells are constantly subjected to pressure-induced cyclic strain. Reactive oxygen species (ROS) have been implicated in atherosclerosis and vascular remodeling. Recent evidence indicates that a vascular NAD(P)H oxidase may be an important source of ROS in both physiologic and pathophysiologic situations. The aim of this study was to investigate cyclic strain-induced NAD(P)H oxidase activity in endothelial cells. ROS production was examined by electron paramagnetic resonance and lucigenin chemiluminescence. Cyclic strain-induced NAD(P)H oxidase activity was quantified by activity assay while the expression of p22phox was monitored by Northern blotting. Endothelial cells produce basal amounts of ROS that were enhanced by cyclic strain. Moreover subsequent stimulation with TNF-alpha resulted in significantly greater ROS production in cells previously exposed to cyclic strain as compared to static conditions. Cyclic strain resulted in a significant increase in message for the p22phox subunit as well as activity of the NAD(P)H oxidase. The induced oxidative stress was accompanied by increased mobilization of the transcription factor NFkappaB, an effect that was blocked by a pharmacological inhibitor of NAD(P)H. These results demonstrate a pivotal role for NAD(P)H oxidase in cyclic strain-induced endothelial ROS production and may provide insight into the modulation of vascular disease by biomechanical forces. J. Cell. Biochem. Suppl. 36: 99-106, 2001.
Matsushita
H
H
Division of Cardiovascular Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305-5406, USA.
Lee
K H
KH
Tsao
P S
PS
D015152:Blotting, Northern; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D026901:Membrane Transport Proteins; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019255:NADPH Oxidases; D016328:NF-kappa B / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology
D026901:Membrane Transport Proteins; D016328:NF-kappa B; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase