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

International Journal of Molecular Sciences

Koichi Yoshimura³  Ayako Nagasawa³  Junichi Kudo³  Masahiko Onoda³  Noriyasu Morikage³  Akira Furutani³  Hiroki Aoki¹  Kimikazu Hamano³  Jonathan Golledge² 

[1] Cardiovascular Research Institute, Kurume University, Kurume 830-0011, Japan; E-Mail:Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan;;Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan; E-Mails:

关键词: statin;    abdominal aortic aneurysm;    nuclear factor-κB;   

DOI  :  10.3390/ijms160511213

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.