Expression of NADH/NADPH oxidase p22phox in human coronary arteries

Expression of NADH/NADPH oxidase p22phox in human coronary arteries
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DOI:
10.1161/01.cir.100.14.1494
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发表时间:
1999-10-05
期刊:
影响因子:
37.8
通讯作者:
Yokoyama, M
Yokoyama, M
中科院分区:
医学1区
文献类型:
--
作者:
Azumi, H;Inoue, N;Yokoyama, M

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背景-NADH/NADPH 氧化酶是脉管系统中超氧化物的重要来源。最近,我们发现该氧化酶的关键成分 p22(phox) 基因的多态性与冠状动脉疾病的风险相关。本研究的目的是调查p22(phox)在人冠状动脉中的定位,并检查其在非动脉粥样硬化和动脉粥样硬化冠状动脉中表达的差异。方法与结果-使用尸检病例(n=11)的冠状动脉切片,通过免疫组织化学和Western blotting检测p22(phox)的表达,在非动脉粥样硬化冠状动脉中 动脉中,p22(phox)表达较弱,主要在外膜。在动脉粥样硬化冠状动脉中,在细胞过多区域和肩部区域的新内膜和内侧平滑肌细胞以及浸润巨噬细胞中检测到强烈的免疫反应性。半定量分析和Western blotting结果显示,p22(phox)在动脉粥样硬化的冠状动脉中的表达较非动脉粥样硬化的动脉更为明显。双重染色显示p22(phox)在外膜成纤维细胞、平滑肌细胞、新内膜和中膜中的巨噬细胞以及内皮细胞中表达。结论——随着动脉粥样硬化的进展,p22(phox)通过血管壁的表达增加。 p22(phox)可能参与动脉粥样硬化性冠状动脉疾病的发病机制和病理生理学。
Background-NADH/NADPH oxidase is an important source of superoxide in the vasculature. Recently, we found that polymorphism of the gene p22(phox), a critical component of this oxidase, is associated with a risk of coronary artery disease; The aim of this study was to investigate the localization of p22(phox) in human coronary arteries and to examine its difference in expression between nonatherosclerotic and atherosclerotic coronary arteries.Methods ana Results-Using coronary artery sections from autopsied cases (n=11), the expression of p22(phox) was examined by immunohistochemistry and Western blotting, In nonatherosclerotic coronary arteries, p22(phox) was weakly expressed, mainly in the adventitia. In atherosclerotic coronary arteries, intensive immunoreactivity was detected in neointimal and medial smooth muscle cells and infiltrating macrophages in hypercellular regions and at the shoulder region. Semiquantitative analysis and Western blotting showed that the expression of p22(phox) in atherosclerotic coronary arteries was more pronounced than that in nonatherosclerotic arteries. Double staining revealed p22(phox) expression in adventitial fibroblasts, smooth muscle cells, macrophages in the neointima and media, and endothelial cells.Conclusions-As atherosclerosis progressed, the expression of p22(phox) increased through the vessel wall. p22(phox) might participate in the pathogenesis and pathophysiology of atherosclerotic coronary disease.