Oxidative stress in the pathogenesis of thoracic aortic aneurysm: Protective role of statin and angiotensin II type 1 receptor blocker

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 p22(phox)-based NADH/NADPH oxidase in the pathogenesis ofTAA. Methods: Human thoracic aneurysmal (11-40) and non-aneurysinal (control, n=39) aortic sections were examined, and the localization of p22(phox), 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 p22(phox) expression was investigated by multiple regression analysis. Results: In situ production of ROS and the expression of p22(phox) increased markedly in TAA throughout the wall, and Western blot confirmed the enhanced expression of p22(phox), 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 p22(phox). Multiple regression analysis revealed that medical treatment with statin and angiotensin II type 1 receptor blocker (ARB) suppressed p22(phox) expression in TAA. Conclusion: Our findings indicate the role of' p22(phox)-based NADH/NADPH oxidase and the local renin-angiotensin system in the pathogenesis of TAA. Statin and ARB might have inhibitor effects on the formation of aneurysms y via the suppression of NADH/NADPH oxidase. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.