Simvastatin decreases free radicals formation in the human abdominal aortic aneurysm wall via NF-κB.

Abstract

OBJECTIVES:

Statins have been reported to suppress the progression of abdominal aortic aneurysm (AAA). However, the effects of statins on inflammatory processes and free radicals generation are poorly understood.

METHODS:

Wall samples from 51 patients (simvastatin patients, n = 34; non-statin patients, n = 17; matched by sex, age and aneurysm size) subjected to elective open AAA repair were analysed. We examined the effects of simvastatin on lipid peroxidation (4-hydroxy-trans-2-nonenal (4-HNE)), hydrogen peroxide (H(2)O(2)), tumour necrosis factor alpha (TNF-α) concentration, superoxide dismutase (SOD) and catalase (CAT) activity as well as nuclear factor kappa B (NF-κB) pathway activation in human AAA wall samples.

RESULTS:

Treatment with simvastatin resulted in a decrease in 4-HNE and TNF-α concentration (median 4.18 μg/mg protein vs. 4.75, p = 0.012; median 10.33 pg/ml vs. 11.81, p = 0.026, respectively). CAT activity was higher in the simvastatin group (median 3.98 U ml vs. 3.19, p = 0.023). NF-κB expression was lower (p = 0.018) in the simvastatin group. However, simvastatin had little effect on H(2)O(2) concentration (p = 0.832) and SOD activity (p = 0.401).

CONCLUSION:

Simvastatin inhibits free radicals and TNF-α generation and improves antioxidant capacity of human AAA wall tissue, possibly through the suppression of NF-κB activity. This may be one possible explanation how statins can inhibit AAA oxidative stress.

• Authors: A Piechota-Polanczyk, A Goraca, S Demyanets, M Mittlboeck, C Domenig, C Neumayer, J Wojta, J Nanobachvili, I Huk, M Klinger
• Journal: European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery (Eur J Vasc Endovasc Surg) Vol. 44 Issue 2 Pg. 133-7 (Aug 2012) ISSN: 1532-2165 [Electronic] England
• PMID: 22694979 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Aldehydes
• Antioxidants
• Free Radicals
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Simvastatin
• Hydrogen Peroxide
• Catalase
• Superoxide Dismutase
• 4-hydroxy-2-nonenal

Topics

• Aged
• Aged, 80 and over
• Aldehydes (analysis)
• Antioxidants (therapeutic use)
• Aorta, Abdominal (chemistry, drug effects, surgery)
• Aortic Aneurysm, Abdominal (drug therapy, metabolism, surgery)
• Austria
• Case-Control Studies
• Catalase (analysis)
• Female
• Free Radicals (analysis)
• Humans
• Hydrogen Peroxide (analysis)
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Lipid Peroxidation (drug effects)
• Male
• Middle Aged
• NF-kappa B (analysis)
• Oxidative Stress (drug effects)
• Signal Transduction (drug effects)
• Simvastatin (therapeutic use)
• Superoxide Dismutase (analysis)
• Tumor Necrosis Factor-alpha (analysis)