The complex biological processes associated with abdominal aortic aneurysm (AAA) include oxidative stress and proteolysis in relation to both leukocyte recruitment and platelet activation, leading to immuno-inflammatory response, cell death and extracellular matrix breakdown. A key player in regulating immune-inflammatory processes is nuclear factor-κB (NF-κB), a redox-sensitive transcription factor involved in the transmission of various signals from the cytoplasm to the nucleus of numerous cell types, activating genes which codify products such as adhesion molecules, chemoattractants, proinflammatory enzymes and procoagulant proteins. Piechota's paper confirms that NF-κB could be involved in the pathogenesis of AAA, as suggested by previous data.
- Nakashima H.
- Aoki M.
- Miyake T.
- Kawasaki T.
- Iwai M.
- Jo N.
- et al.
Inhibition of experimental abdominal aortic aneurysm in the rat by use of decoy oligodeoxynucleotides suppressing activity of nuclear factor kappaB and ets transcription factors.
Circulation. 2004; 109: 132-138
Statins have proved the greatest impact on cardiovascular disease since aspirin. Their pleiotropic effects beyond lipid lowering are still being researched. Recent findings suggest that the clinical benefit of these drugs could be related to a reduction in oxidative stress, blood thrombogenicity and to anti-inflammatory and immunomodulatory properties. Piechota et al offer new interesting data on the effect of simvastatin on inflammation and free radicals generation within the aortic wall. The current results are somewhat baffling, as the authors have obtained an increase in catalase activity, and a decrease in TNFα concentration and NF-kB expression in the AAA wall samples treated with simvastatin, but not superoxide dismutase (SOD) activity or H2O2. This is not the first study to show a significant inhibition of statins on both NF-kB activity
2and oxidant enzymes such as NADPH oxidase and myeloperoxidase,
- Kalyanasundaram A.
- Elmore J.R.
- Manazer J.R.
- Golden A.
- Franklin D.P.
- Galt S.W.
- et al.
Simvastatin suppresses experimental aortic aneurysm expansion.
J Vasc Surg. 2006; 43: 117-124
3as well as an up-regulation of the activity of antioxidant enzymes such as catalase.
- Kumar A.P.
- Reynolds W.F.
Statins downregulate myeloperoxidase gene expression in macrophages.
Biochem Biophys Res Commun. 2005; 331: 442-451
4However, none have obtained an absolute reduction in the tissue's oxidative end-products, such as H2O2. These are indeed difficult to quantify and often the net effect must be extrapolated indirectly, through the evaluation of the activity of oxidant or antioxidant enzymes. Still, the exact mechanism remains unclear.
- Ota H.
- Eto M.
- Kano M.R.
- Kahyo T.
- Setou M.
- Ogawa S.
- et al.
Induction of endothelial nitric oxide synthase, SIRT1, and catalase by statins inhibits endothelial senescence through the Akt pathway.
Arterioscler Thromb Vasc Biol. 2010; 30: 2205-2211
The reduction in the incidence of cardiovascular events and death associated with statins has been sufficiently proved and current guidelines recommend that all vascular patients, unless specifically contraindicated, should receive the drug. But the evidence of its impact on AAA growth and rupture risk is still weak, level B and C at best, with contradictory published results. Studies aiming to better understand the therapeutical effects of statins are timely and welcome.
- Inhibition of experimental abdominal aortic aneurysm in the rat by use of decoy oligodeoxynucleotides suppressing activity of nuclear factor kappaB and ets transcription factors.Circulation. 2004; 109: 132-138
- Simvastatin suppresses experimental aortic aneurysm expansion.J Vasc Surg. 2006; 43: 117-124
- Statins downregulate myeloperoxidase gene expression in macrophages.Biochem Biophys Res Commun. 2005; 331: 442-451
- Induction of endothelial nitric oxide synthase, SIRT1, and catalase by statins inhibits endothelial senescence through the Akt pathway.Arterioscler Thromb Vasc Biol. 2010; 30: 2205-2211
Published online: May 22, 2012
© 2012 European Society for Vascular Surgery. Published by Elsevier Inc.
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