IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2010;2(2):111-124

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

Mitsuru Ohishi, Gregory J. Dusting, Paul A. Fennessy, Frederick A.O. Mendelsohn, Xiao C. Li, Jia L. Zhuo

Department of Geriatric Medicine, Osaka University Medical School, Osaka, Japan; Howard Florey Institute of Experimental Physiology
and Medicine, The University of Melbourne, Victoria 3010, Australia; and Division of Hypertension and Vascular Research, Department
of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202, USA

Received April 16, 2010, accepted April 22, 2010, available online April 30, 2010

Abstract: 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 proatherosclerotic
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 antiatherosclerotic 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. (IJPPP1004001).

Key words: Atherosclerosis, angiotensin converting enzyme, angiotensin II, human coronary artery, nitric oxide synthase,

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Address all correspondence to:
Jia L. Zhuo, MD, PhD
Division of Hypertension and Vascular Research
Department of Internal Medicine Henry Ford Hospital
2799 West Grand Blvd, Detroit, MI 48202.
Tel: (313) 916-4115, Fax: (313) 916-9055