Mechanisms of oxidative stress in human aortic aneurysms — association with clinical risk factors for atherosclerosis and disease severity

Guzik, B. et al. (2013) Mechanisms of oxidative stress in human aortic aneurysms — association with clinical risk factors for atherosclerosis and disease severity. International Journal of Cardiology, 168(3), pp. 2389-2396. (doi: 10.1016/j.ijcard.2013.01.278) (PMID:23506637) (PMCID:PMC3819986)

Abstract

Aortic abdominal aneurysms (AAA) are important causes of cardiovascular morbidity and mortality. Oxidative stress may link multiple mechanisms of AAA including vascular inflammation and increased metalloproteinase activity. However, the mechanisms of vascular free radical production remain unknown. Accordingly, we aimed to determine sources and molecular regulation of vascular superoxide (O2radical dot−) production in human AAA. Methods and results: AAA segments and matched non-dilated aortic samples were obtained from 40 subjects undergoing AAA repair. MDA levels (determined by HPLC/MS) were greater in plasma of AAA subjects (n = 16) than in risk factor matched controls (n = 16). Similarly, superoxide production, measured by lucigenin chemiluminescence and dihydroethidium fluorescence, was increased in aneurysmatic segments compared to non-dilated aortic specimens. NADPH oxidases and iNOS are the primary sources of O2radical dot− in AAA. Xanthine oxidase, mitochondrial oxidases and cyclooxygenase inhibition had minor or no effect. Protein kinase C inhibition had no effect on superoxide production in AAA. NADPH oxidase subunit mRNA levels for p22phox, nox2 and nox5 were significantly increased in AAAs while nox4 mRNA expression was lower. Superoxide production was higher in subjects with increased AAA repair risk Vanzetto score and was significantly associated with smoking, hypercholesterolemia and presence of CAD in AAA cohort. Basal superoxide production and NADPH oxidase activity were correlated to aneurysm size. Conclusions: Increased expression and activity of NADPH oxidases are important mechanisms underlying oxidative stress in human aortic abdominal aneurysm. Uncoupled iNOS may link oxidative stress to inflammation in AAA. Oxidative stress is related to aneurysm size and major clinical risk factors in AAA patients.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Guzik, Professor Tomasz and Guzik, Dr Bartlomiej
• Authors: Guzik, B., Sagan, A., Ludew, D., Mrowiecki, W., Chwała, M., Bujak-Gizycka, B., Filip, G., Grudzien, G., Kapelak, B., Żmudka, K., Mrowiecki, T., Sadowski, J., Korbut, R., and Guzik, T. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: International Journal of Cardiology
• Publisher: Elsevier
• ISSN: 0167-5273
• ISSN (Online): 1874-1754
• Published Online: 15 March 2013
• Copyright Holders: Crown Copyright © 2013
• First Published: First published in International Journal of Cardiology 168(3):2389-2396
• Publisher Policy: Reproduced under a Creative Commons License