Increased expression and co-localization of ACE, angiotensin II AT1 receptors and inducible nitric oxide synthase in atherosclerotic human coronary arteries

International Journal of Physiology, Pathophysiology and Pharmacology

Xiao C Li¹  Mitsuru Ohishi¹  Gregory J Dusting¹  Frederick AO Mendelsohn¹  Paul A Fennessy¹  Jia L Zhuo¹ 

关键词: Atherosclerosis;    angiotensin converting enzyme;    angiotensin II;    human coronary artery;    nitric oxide synthase;    immunohistochemistry;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

Using immunohistochemistry and quantitative in vitro autoradiography, the present study was undertaken to examine whether co-expression of pro-atherosclerotic factors, ACE, the AT₁ receptor, and iNOS, is increased in early and advanced atherosclerotic lesions of human coronary arteries. In normal coronary arteries, ACE and eNOS were strongly co-expressed in endothelial cells (ECs), whereas the AT₁ receptor was expressed in medial smooth muscle cells (SMCs). By contrast, iNOS was not expressed in ECs and SMCs. In early atherosclerotic lesions and atheromatous plaques, ACE, the AT₁ receptor and iNOS immunostaining were primarily co-localized in infiltrated macrophages and SMCs adjacent to macrophages. eNOS expression was lower in ECs than in normal arteries, and absent in accumulated macrophages and SMCs. In fibrosclerotic plaques, ACE, the AT₁ receptor, and iNOS immunostaining were still positive in macrophages as well as new microvessels within the plaques. Interestingly, SMCs in vasa vasorum of the adventitia in atheromatous and fibrosclerotic plaques were also strongly positive for AT₁ receptor and iNOS, while ECs of the vasa vasorum were positive for ACE and eNOS. The present study demonstrates that multiple pro-atherosclerotic factors ACE, AT₁ receptor and iNOS are co-localized almost exclusively in infiltrated macrophages and SMCs that have accumulated in or adjacent to early and advanced atherosclerotic plaques, while the anti-atherosclerotic enzyme eNOS is reduced in ECs. These data therefore suggest that increased formation of Ang II and iNOS in infiltrated macrophages and medial SMCs might well play important roles in the development and progression of human coronary atherosclerosis.

【 授权许可】

Unknown