Azumi H, Inoue N, Takeshita S, Rikitake Y, Kawashima S, Hayashi Y, Itoh H, Yokoyama M
First Department of Internal Medicine, Kobe University School of Medicine, Kobe, Japan.
Circulation. 1999 Oct 5;100(14):1494-8. doi: 10.1161/01.cir.100.14.1494.
NADH/NADPH oxidase is an important source of superoxide in the vasculature. Recently, we found that polymorphism of the gene p22phox, 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 p22phox in human coronary arteries and to examine its difference in expression between nonatherosclerotic and atherosclerotic coronary arteries.
Using coronary artery sections from autopsied cases (n=11), the expression of p22phox was examined by immunohistochemistry and Western blotting. In nonatherosclerotic coronary arteries, p22phox 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 p22phox in atherosclerotic coronary arteries was more pronounced than that in nonatherosclerotic arteries. Double staining revealed p22phox expression in adventitial fibroblasts, smooth muscle cells, macrophages in the neointima and media, and endothelial cells.
As atherosclerosis progressed, the expression of p22phox increased through the vessel wall. p22phox might participate in the pathogenesis and pathophysiology of atherosclerotic coronary disease.
NADH/NADPH氧化酶是血管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p22phox基因的多态性与冠状动脉疾病风险相关。本研究的目的是调查p22phox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之间表达的差异。
使用尸检病例的冠状动脉切片(n = 11),通过免疫组织化学和蛋白质印迹法检测p22phox的表达。在非动脉粥样硬化冠状动脉中,p22phox表达较弱,主要在外膜。在动脉粥样硬化冠状动脉中,在新生内膜和中膜平滑肌细胞以及高细胞区域和肩部区域浸润的巨噬细胞中检测到强烈的免疫反应性。半定量分析和蛋白质印迹显示,p22phox在动脉粥样硬化冠状动脉中的表达比在非动脉粥样硬化动脉中更明显。双重染色显示p22phox在外膜成纤维细胞、平滑肌细胞、新生内膜和中膜的巨噬细胞以及内皮细胞中表达。
随着动脉粥样硬化的进展,p22phox的表达在整个血管壁中增加。p22phox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。