Increased expression and co-localization of ACE, angiotensin II AT(1) receptors and inducible nitric oxide synthase in atherosclerotic human coronary arteries.
Increased expression and co-localization of ACE, angiotensin II AT(1) receptors and inducible nitric oxide synthase in atherosclerotic human coronary arteries.
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发表时间：
2010-04
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通讯作者：
M. Ohishi;G. Dusting;P. Fennessy;F. Mendelsohn;X. Li;J. Zhuo
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作者：
M. Ohishi;G. Dusting;P. Fennessy;F. Mendelsohn;X. Li;J. Zhuo
采用免疫组织化学和定量体外放射自显影，本研究旨在检测促动脉粥样硬化因子ACE、AT（1）受体和iNOS的共同表达是否在人冠状动脉早期和晚期动脉粥样硬化病变中增加。在正常冠状动脉中，ACE和eNOS在内皮细胞（EC）中强烈共表达，而AT（1）受体在中膜平滑肌细胞（SMC）中表达。而内皮细胞和平滑肌细胞不表达iNOS。在早期动脉粥样硬化病变和动脉粥样硬化斑块中，ACE、AT（1）受体和iNOS免疫染色主要共同定位于浸润的巨噬细胞和邻近巨噬细胞的SMC中。内皮细胞中eNOS表达低于正常动脉，积聚的巨噬细胞和SMC中eNOS表达缺失。在纤维硬化斑块中，ACE、AT（1）受体和iNOS免疫染色在巨噬细胞以及斑块内的新生微血管中仍呈阳性。有趣的是，动脉粥样硬化和纤维硬化斑块外膜血管中的SMC也呈AT（1）受体和iNOS强阳性，而血管内皮细胞则呈ACE和eNOS阳性。目前的研究表明，多种促动脉粥样硬化因子ACE，AT（1）受体和iNOS几乎只在浸润的巨噬细胞和SMC中共同定位，这些巨噬细胞和SMC积聚在早期和晚期动脉粥样硬化斑块中或附近，而抗动脉粥样硬化酶eNOS在EC中减少。因此，这些数据表明，在浸润的巨噬细胞和中膜SMCs中增加的Ang II和iNOS的形成可能在人类冠状动脉粥样硬化的发展和进展中发挥重要作用。
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.