Oscillatory and steady laminar shear stress differentially affect human endothelial redox state - Role of a superoxide-producing NADH oxidase
Oscillatory and steady laminar shear stress differentially affect human endothelial redox state - Role of a superoxide-producing NADH oxidase
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DOI：
10.1161/01.res.82.10.1094
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发表时间：
1998-06-01
影响因子：
20.1
通讯作者：
Griendling, KK
中科院分区：
文献类型：
--
作者：
De Keulenaer, GW;Chappell, DC;Griendling, KK
动脉粥样硬化病变位于低切应力和振荡血流部位，与血管分流板相对。由于病变中突出的内皮致炎基因受氧化敏感的转录调控机制的调节，我们检测了培养的人脐静脉内皮细胞在振荡或稳定的层流剪切应力下的氧化还原状态。通过检测产生超氧化物(O-2(.-))的NADH氧化酶(血管细胞内活性氧的主要来源)的活性、细胞内O-2(.-)水平、氧化还原敏感基因血红素加氧酶-1(HO-1)的诱导以及铜/锌超氧化物歧化酶(铜/锌超氧化物歧化酶)的含量来评估内皮氧化应激。铜/锌超氧化物歧化酶是一种抗氧化防御酶，其表达水平适应氧化应激的变化。当细胞暴露于振荡切变(+/-5达因/厘米(2)，1赫兹)1、5和24小时时，NADH氧化酶活性和HO-1含量逐渐增加，最高可达174+/-16%(P
Atherosclerotic lesions are found opposite vascular flow dividers at sites of low shear stress and oscillatory flow. Since endothelial proinflammatory genes prominent in lesions are regulated by oxidation-sensitive transcriptional control mechanisms, we examined the redox state of cultured human umbilical vein endothelial cells after either oscillatory or steady laminar fluid shear stress. Endothelial oxidative stress was assessed by measuring activity of the superoxide (O-2(.-))-producing NADH oxidase (a major source of reactive oxygen species in vascular cells), intracellular O-2(.-) levels, induction of the redox-sensitive gene heme oxygenase-1 (HO-1), and abundance of Cu/Zn superoxide dismutase (Cu/Zn SOD), an antioxidant defense enzyme whose level of expression adapts to changes in oxidative stress. When cells were exposed to oscillatory shear (+/-5 dyne/cm(2), 1 Hz) for 1, 5, and 24 hours, NADH oxidase activity and the amount of HO-1 progressively increased up to 174+/-16% (P