Oscillatory shear stress stimulates endothelial production of O2- from p47phox-dependent NAD(P)H oxidases, leading to monocyte adhesion
Oscillatory shear stress stimulates endothelial production of O2- from p47phox-dependent NAD(P)H oxidases, leading to monocyte adhesion
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DOI：
10.1074/jbc.m305150200
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发表时间：
2003-11-21
影响因子：
4.8
通讯作者：
Jo, H
中科院分区：
文献类型：
--
作者：
Hwang, J;Saha, A;Jo, H
在分支动脉中，振荡剪切（OS）暴露的动脉区域是动脉粥样硬化的易损部位，而层流剪切（LS）暴露的动脉区域相对保护较好。在这里，我们检验了OS和LS不同地调节内皮细胞NAD(P)H氧化酶产生O-2（-）的假设，这反过来又导致了它们对关键的动脉粥样硬化事件（单核细胞粘附）的相反影响。我们使用了从缺乏NAD(P)H氧化酶成分的C57BL/6 （MAE- c57）和p47(phox-/-) （MAE- p47(-/-)）小鼠获得的主动脉内皮细胞。O-2（-）的产生采用双氢乙二铵染色和电子自旋阱电子自旋共振法测定。慢性暴露于动脉水平的OS (+/- 5 dynes/cm(2)) （18 h）使MAE-C57细胞的O-2（-）增加了2倍，单核细胞粘附（3倍），而慢性LS （15 dynes/cm(2), 18 h）与静态条件相比，显著降低了单核细胞粘附和O-2（-）。相比之下，LS和OS均不能诱导O-2（-）的产生和单核细胞粘附MAE- p47（-/-）。用细胞渗透性超氧化物歧化酶化合物（聚乙二醇-超氧化物歧化酶）处理MAE-C57也能抑制os诱导的单核细胞粘附。此外，在MAE-p47（-/-）中过表达p47（phox）可以恢复os诱导的O-2（-）产生和单核细胞粘附。这些结果表明，内皮细胞长期暴露于OS刺激由p47（phox）依赖的NAD(P) H氧化酶产生的O-2（-）和/或其衍生物，进而导致单核细胞粘附，这是早期和关键的动脉粥样硬化事件。
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.