title: Increased expression and co-localization of ACE, angiotensin II AT(1) receptors and inducible nitric oxide synthase in atherosclerotic human coronary arteries.
abstract: Using immunohistochemistry and quantitative in vitro autoradiography, the present study was undertaken to examine whether co-expression of pro-atherosclerotic factors, ACE, the AT(1) 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 AT(1) 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 AT(1) 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 AT(1) 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 AT(1) 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, AT(1) 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.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ohishi
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dusting
authors.forename: Paul A
authors.initials: PA
authors.lastname: Fennessy
authors.forename: Frederick Ao
authors.initials: FA
authors.lastname: Mendelsohn
authors.forename: Xiao C
authors.initials: XC
authors.lastname: Li
authors.forename: Jia L
authors.initials: JL
authors.lastname: Zhuo