期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 278, 期 47, 页码 47291-47298出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M305150200
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资金
- NHLBI NIH HHS [HL 71014, HL 67413] Funding Source: Medline
- NIGMS NIH HHS [T32 GM008169] Funding Source: Medline
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.
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