Journal Article

Oxidative stress in the pathogenesis of thoracic aortic aneurysm

Junya Ejiri, Nobutaka Inoue, Takuro Tsukube, Takashi Munezane, Yutaka Hino, Seiichi Kobayashi, Ken-ichi Hirata, Seinosuke Kawashima, Shinobu Imajoh-Ohmi, Yoshitake Hayashi, Hiroshi Yokozaki, Yutaka Okita and Mitsuhiro Yokoyama

in Cardiovascular Research

Published on behalf of European Society of Cardiology

Volume 59, issue 4, pages 988-996
Published in print October 2003 | ISSN: 0008-6363
Published online October 2003 | e-ISSN: 1755-3245 | DOI:
Oxidative stress in the pathogenesis of thoracic aortic aneurysm

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Objective: The pathogenesis of thoracic aortic aneurysms (TAA) is still unclear. A recent investigation indicated that angiotensin II, a potent activator of NADH/NADPH oxidase, plays an important role in aneurysmal formation. We investigated the potential role of p22phox-based NADH/NADPH oxidase in the pathogenesis of TAA. Methods: Human thoracic aneurysmal (n=40) and non-aneurysmal (control, n=39) aortic sections were examined, and the localization of p22phox, an essential component of the oxidase, and its expressional differences were investigated by immunohistochemistry and Western blot. In situ reactive oxygen species (ROS) generation was examined by the dihydroethidium method, and the impact of medical treatment on p22phox expression was investigated by multiple regression analysis. Results: In situ production of ROS and the expression of p22phox increased markedly in TAA throughout the wall, and Western blot confirmed the enhanced expression of p22phox. The expression was more intense in the regions where monocytes/macrophages accumulated. In these inflammatory regions, numerous chymase-positive mast cells and angiotensin converting enzyme-positive macrophages were present. Their localization closely overlapped the in situ activity of matrix metalloproteinase and the expression of p22phox. Multiple regression analysis revealed that medical treatment with statin and angiotensin II type 1 receptor blocker (ARB) suppressed p22phox expression in TAA. Conclusion: Our findings indicate the role of p22phox-based NADH/NADPH oxidase and the local renin–angiotensin system in the pathogenesis of TAA. Statin and ARB might have inhibitory effects on the formation of aneurysms via hrough the suppression of NADH/NADPH oxidase.

Keywords: Atherosclerosis; Histo(patho)logy; Renin angiotensin system; Statins; NADPH oxidase; ACE, angiotensin converting enzyme; Ang II, angiotensin II; ARB, angiotensin II type 1 receptor blocker; CABG, coronary artery bypass graft surgery; CRP, C-reactive protein; MMP, matrix metalloproteinase; ROS, reactive oxygen species; SMC, smooth muscle cell; TAA, thoracic aortic aneurysms

Journal Article.  5090 words.  Illustrated.

Subjects: Cardiovascular Medicine

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