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Int. J. Mol. Sci. 2015, 16(5), 11213-11228; doi:10.3390/ijms160511213

Inhibitory Effect of Statins on Inflammation-Related Pathways in Human Abdominal Aortic Aneurysm Tissue

1
Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan
2
Graduate School of Health and Welfare, Yamaguchi Prefectural University, Yamaguchi 753-8502, Japan
3
Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Science, Niigata 951-8510, Japan
4
Cardiovascular Research Institute, Kurume University, Kurume 830-0011, Japan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editors: Jonathan Golledge and Joseph V. Moxon
Received: 26 January 2015 / Revised: 27 March 2015 / Accepted: 30 March 2015 / Published: 18 May 2015
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
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Abstract

HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors (statins) have been suggested to attenuate abdominal aortic aneurysm (AAA) growth. However, the effects of statins in human AAA tissues are not fully elucidated. The aim of this study was to investigate the direct effects of statins on proinflammatory molecules in human AAA walls in ex vivo culture. Simvastatin strongly inhibited the activation of nuclear factor (NF)-κB induced by tumor necrosis factor (TNF)-α in human AAA walls, but showed little effect on c-jun N-terminal kinase (JNK) activation. Simvastatin, as well as pitavastatin significantly reduced the secretion of matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-2 and epithelial neutrophil-activating peptide (CXCL5) under both basal and TNF-α-stimulated conditions. Similar to statins, the Rac1 inhibitor NSC23766 significantly inhibited the activation of NF-κB, accompanied by a decreased secretion of MMP-9, MCP-2 and CXCL5. Moreover, the effect of simvastatin and the JNK inhibitor SP600125 was additive in inhibiting the secretion of MMP-9, MCP-2 and CXCL5. These findings indicate that statins preferentially inhibit the Rac1/NF-κB pathway to suppress MMP-9 and chemokine secretion in human AAA, suggesting a mechanism for the potential effect of statins in attenuating AAA progression. View Full-Text
Keywords: statin; abdominal aortic aneurysm; nuclear factor-κB statin; abdominal aortic aneurysm; nuclear factor-κB
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Yoshimura, K.; Nagasawa, A.; Kudo, J.; Onoda, M.; Morikage, N.; Furutani, A.; Aoki, H.; Hamano, K. Inhibitory Effect of Statins on Inflammation-Related Pathways in Human Abdominal Aortic Aneurysm Tissue. Int. J. Mol. Sci. 2015, 16, 11213-11228.

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