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

Eur J Vasc Endovasc Surg. 2012 Aug;44(2):133-7. doi: 10.1016/j.ejvs.2012.04.020. Epub 2012 Jun 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aldehydes / analysis
  • Antioxidants / therapeutic use*
  • Aorta, Abdominal / chemistry
  • Aorta, Abdominal / drug effects*
  • Aorta, Abdominal / surgery
  • Aortic Aneurysm, Abdominal / drug therapy*
  • Aortic Aneurysm, Abdominal / metabolism
  • Aortic Aneurysm, Abdominal / 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

Substances

  • 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