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


CONCLUSIONS
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.
Department of Surgery, Medical University of Vienna, Vienna, Austria.
A
A
Piechota-Polanczyk
A
A
Goraca
S
S
Demyanets
M
M
Mittlboeck
C
C
Domenig
C
C
Neumayer
J
J
Wojta
J
J
Nanobachvili
I
I
Huk
M
M
Klinger
D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000032:analysis; D000975:Antioxidants / Q000627:therapeutic use*; D001012:Aorta, Abdominal / Q000737:chemistry / Q000187:drug effects* / Q000601:surgery; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D001317:Austria; D016022:Case-Control Studies; D002374:Catalase / Q000032:analysis; D005260:Female; D005609:Free Radicals / Q000032:analysis*; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis*; D018384:Oxidative Stress / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D019821:Simvastatin / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000447:Aldehydes; D000975:Antioxidants; D005609:Free Radicals; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019821:Simvastatin; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; C027576:4-hydroxy-2-nonenal