Increased epidermal growth factor-like ligands are associated with elevated vascular nicotinamide adenine dinucleotide phosphate oxidase in a primate model of atherosclerosis.
Increased epidermal growth factor-like ligands are associated with elevated vascular nicotinamide adenine dinucleotide phosphate oxidase in a primate model of atherosclerosis.
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DOI：
10.1161/atvbaha.112.256107
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发表时间：
2012-10
期刊：
影响因子：
--
通讯作者：
Miller FJ Jr
中科院分区：
文献类型：
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作者：
Stanic B;Pandey D;Fulton DJ;Miller FJ Jr
在灵长类动物动脉粥样硬化模型中，描述EGF样配体表达与血管NADPH氧化酶表达和活性之间的关系。成年雄性食蟹猴喂食正常或致动脉粥样硬化（AS）饮食45个月，之后AS组动物喂食正常饮食8个月（回归）。AS饮食动物动脉中膜相关EGF样配体的表达增加，回归组正常化。EGF样配体分布在整个动脉粥样硬化血管，但主要是与巨噬细胞共定位。与配体脱落一致，循环肝素结合EGF升高AS猴血浆中，但不是在回归饮食。动脉粥样硬化与表皮生长因子受体（EGFR）信号的激活有关。NADPH氧化酶亚基Nox 1和Nox 2的表达增加，但不Nox 4或Nox 5的动脉从猴子的AS饮食和回归正常。Nox 1和Nox 2水平与EGF样配体呈正相关。在培养的猴平滑肌细胞中，用EGF样配体处理增加了Nox 1的表达和活性。这些数据确定EGF样配体作为动脉粥样硬化形成的潜在调节剂，部分原因是血管NADPH氧化酶活性增加。
To characterize the relationship between expression of EGF-like ligands and vascular NADPH oxidase expression and activity in a primate model of atherosclerosis. Adult male Cynomolgus monkeys were fed a normal or atherogenic (AS) diet for 45 months, after which animals from the AS group were placed on a normal diet for 8 months (regression). Expression of membrane-associated EGF-like ligands was increased in arteries from animals on the AS diet and normalized in the regression group. EGF-like ligands were distributed throughout atherosclerotic vessels but predominantly co-localized with macrophages. Consistent with ligand shedding, circulating heparin bound-EGF was elevated in plasma of AS monkeys but not in those on regression diet. Atherosclerosis was associated with activation of EGF receptor (EGFR) signaling. Expression of NADPH oxidase subunits Nox1 and Nox2 but not Nox4 or Nox5 was increased in arteries from monkeys on the AS diet and returned to normal with regression. Levels of Nox1 and Nox2 positively correlated with EGF-like ligands. In cultured monkey smooth muscle cells, treatment with EGF-like ligands increased Nox1 expression and activity. These data identify EGF-like ligands as potential modulators of atherogenesis due in part to increased vascular NADPH oxidase activity.