Overweight and obese humans demonstrate increased vascular endothelial NAD(P)H oxidase-p47phox expression and evidence of endothelial oxidative stress
Overweight and obese humans demonstrate increased vascular endothelial NAD(P)H oxidase-p47phox expression and evidence of endothelial oxidative stress
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DOI：
10.1161/circulationaha.106.657486
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发表时间：
2007-02-06
期刊：
影响因子：
37.8
通讯作者：
Seals, Douglas R.
中科院分区：
文献类型：
--
作者：
Silver, Annemarie E.;Beske, Stacy D.;Seals, Douglas R.
背景-肥胖可能改变血管内皮细胞蛋白表达（VECPE）的分子，影响动脉粥样硬化的易感性。方法和结果-对108例无临床疾病的男性和女性的血管内皮细胞进行定量免疫荧光检测，这些男性和女性在肥胖方面差异很大（体重指数18.4至36.7 kg/m2;全身脂肪5.8至55.0 kg;腰围：63.0至122.9 cm）。3种肥胖症的表达均与氧化酶亚基NAD（P）H氧化酶-p47（phox）的VECPE呈正相关（部分相关系数r = 0.22 ~ 0.24，P均< 0.05），与抗氧化酶过氧化氢酶的VECPE呈正相关（r =0.71 ~ 0.75，P均< 0.001）。总体脂与硝基酪氨酸的VECPE呈正相关（r（部分）=0.36，P=0.003），这是一种蛋白质氧化的标志物，在男性中，与Ser 1177-磷酸化内皮型一氧化氮合酶（r（部分）=0.46，P=0.02），一种激活形式的内皮型一氧化氮合酶。超重/肥胖受试者（体重指数>= 25 kg/m2）的人的NAD（P）H氧化酶-47（phox）、硝基酪氨酸、过氧化氢酶和胞质抗氧化剂CuZn超氧化物歧化酶的VECPE高出35%至130（均P < 0.05），同时，与正常体重受试者（体重指数< 25 kg/m2）相比，有效的局部血管收缩剂内皮素-1（endothelin-1）的VECPE高56%（P=0.05）。核因子-κ B蛋白的表达在最肥胖的成人中比最瘦的成人高60%到100%（P
Background - Obesity may alter vascular endothelial cell protein expression (VECPE) of molecules that influence susceptibility to atherosclerosis.Methods and Results - Quantitative immunofluorescence was performed on vascular endothelial cells collected from 108 men and women free of clinical disease who varied widely in adiposity (body mass index 18.4 to 36.7 kg/m(2); total body fat 5.8 to 55.0 kg; waist circumference: 63.0 to 122.9 cm). All 3 expressions of adiposity were positively associated with VECPE of the oxidant enzyme subunit NAD(P)H oxidase-p47(phox) (part correlation coefficient [r(part)] 0.22 to 0.24, all P < 0.05) and the antioxidant enzyme catalase (r(part)=0.71 to 0.75, all P < 0.001). Total body fat was positively associated with VECPE of nitrotyrosine (r(part)=0.36, P=0.003), a marker of protein oxidation, and, in men, with Ser1177-phosphorylated endothelial nitric oxide synthase (r(part)=0.46, P=0.02), an activated form of endothelial nitric oxide synthase. Overweight/obese subjects (body mass index >= 25 kg/m(2)) had 35% to 130% higher VECPE of NAD(P)H oxidasep-47(phox), nitrotyrosine, catalase, and the cytosolic antioxidant CuZn superoxide dismutase (all P < 0.05), as well as a 56% greater VECPE of the potent local vasoconstrictor endothelin-1 (P=0.05) than normal-weight subjects (body mass index < 25 kg/m(2)). Nuclear factor-kappa B protein expression was approximate to 60% to 100% greater in the most obese adults than in the leanest adults (P