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Oscillatory Shear Stress Stimulates Endothelial Production of O 2 - from p47 -dependent NAD(P)H Oxidases, Leading to Monocyte Adhesion

2003; Elsevier BV; Volume: 278; Issue: 47 Linguagem: Inglês

10.1074/jbc.m305150200

1083-351X

Jinah Hwang, Aniket Saha, Yong Chool Boo, George P. Sorescu, J. Scott McNally, Steven M. Holland, Sergey Dikalov, Don P. Giddens, Kathy K. Griendling, David G. Harrison, Hanjoong Jo,

Neutrophil, Myeloperoxidase and Oxidative Mechanisms

Arterial regions exposed to oscillatory shear (OS) in branched arteries are lesion-prone sites of atherosclerosis, whereas those of laminar shear (LS) are relatively well protected. Here, we examined the hypothesis that OS and LS differentially regulate production of O 2 - from the endothelial NAD(P)H oxidase, which, in turn, is responsible for their opposite effects on a critical atherogenic event, monocyte adhesion. We used aortic endothelial cells obtained from C57BL/6 (MAE-C57) and p47 phox-/- (MAE-p47 -/- ) mice, which lack a component of NAD(P)H oxidase. O 2 - production was determined by dihydroethidium staining and an electron spin resonance using an electron spin trap methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine. Chronic exposure (18 h) to an arterial level of OS (± 5 dynes/cm 2 ) increased O 2 - (2-fold) and monocyte adhesion (3-fold) in MAE-C57 cells, whereas chronic LS (15 dynes/cm 2 , 18 h) significantly decreased both monocyte adhesion and O 2 - compared with static conditions. In contrast, neither LS nor OS were able to induce O 2 - production and monocyte adhesion to MAE-p47 -/- . Treating MAE-C57 with a cell-permeable superoxide dismutase compound, polyethylene glycol-superoxide dismutase, also inhibited OS-induced monocyte adhesion. In addition, over-expressing p47 phox in MAE-p47 -/- restored OS-induced O 2 - production and monocyte adhesion. These results suggest that chronic exposure of endothelial cells to OS stimulates O 2 - and/or its derivatives produced from p47 phox -dependent NAD(P)H oxidase, which, in turn, leads to monocyte adhesion, an early and critical atherogenic event.