Augmented Superoxide Production By Nox2-Containing NADPH Oxidase Causes Cerebral Artery Dysfunction During Hypercholesterolemia
Augmented Superoxide Production By Nox2-Containing NADPH Oxidase Causes Cerebral Artery Dysfunction During Hypercholesterolemia
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DOI：
10.1161/strokeaha.109.575365
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发表时间：
2010-04-01
期刊：
影响因子：
8.3
通讯作者：
Sobey, Christopher G.
中科院分区：
文献类型：
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作者：
Miller, Alyson A.;De Silva, Michael;Sobey, Christopher G.
背景和目的 - 我们测试了这样的假设：高胆固醇血症期间脑动脉中 Nox2-NADPH 氧化酶产生的超氧化物增加，并导致一氧化氮功能下降。方法 - 野生型 (WT)、载脂蛋白 E 缺陷型 (ApoE(-/-)) 和 Nox2(-/-)/ApoE(-/-) 小鼠采用高脂肪饮食喂养 7 至 14 周。使用L-012（100μmol/L）增强化学发光测量脑动脉的基础超氧化物产生。通过收缩器对 N(omega)-硝基-L-精氨酸甲酯（L-NAME；100 μmol/L）的反应来评估离体大脑中动脉的一氧化氮功能。使用蛋白质印迹法测量 Nox2、p47phox、内皮一氧化氮合酶和超氧化物歧化酶的蛋白表达 (1-3)。结果-WT 和 ApoE(-/-) 小鼠的脑动脉形态相似。在 ApoE(-/-) 小鼠中，但在 Nox2(-/-)/ApoE(-/-) 小鼠中，脑动脉产生的超氧化物比 WT 小鼠高约 50%（P
Background and Purpose-We tested the hypothesis that elevated superoxide production by Nox2-NADPH oxidase occurs in cerebral arteries during hypercholesterolemia and causes decreased nitric oxide function.Methods-Wild-type (WT), apolipoprotein E-deficient (ApoE(-/-)) and Nox2(-/-)/ApoE(-/-) mice were fed a high-fat diet for 7 to 14 weeks. Basal superoxide production by cerebral arteries was measured using L-012 (100 mu mol/L)-enhanced chemiluminescence. Nitric oxide function was assessed in isolated middle cerebral arteries through the constrictor response to N(omega)-nitro-L-arginine methyl ester (L-NAME; 100 mu mol/L). Western blotting was used to measure protein expression of Nox2, p47phox, endothelial nitric oxide synthase, and superoxide dismutases (1-3).Results-Morphology of cerebral arteries was similar in WT and ApoE(-/-) mice. In ApoE(-/-), but not Nox2(-/-)/ApoE(-/-) mice, superoxide production by cerebral arteries was approximately 50% greater than in WT mice (P