Expression of NADH/NADPH oxidase p22phox in human coronary arteries.

ABSTRACT

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: As atherosclerosis progressed, the expression of p22phox increased through the vessel wall. p22phox might participate in the pathogenesis and pathophysiology of atherosclerotic coronary disease.