Inhibitory effect of statins on inflammation-related pathways in human abdominal aortic aneurysm tissue

Int J Mol Sci. 2015 May 18;16(5):11213-28. doi: 10.3390/ijms160511213.


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.

Keywords: abdominal aortic aneurysm; nuclear factor-κB; statin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aminoquinolines / pharmacology
  • Anthracenes / pharmacology
  • Aorta, Abdominal / drug effects
  • Aorta, Abdominal / metabolism
  • Aortic Aneurysm, Abdominal / metabolism
  • Aortic Aneurysm, Abdominal / pathology*
  • Chemokine CCL8 / metabolism
  • Chemokine CXCL5 / metabolism
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • In Vitro Techniques
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Pyrimidines / pharmacology
  • Signal Transduction / drug effects*
  • Simvastatin / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • rac1 GTP-Binding Protein / antagonists & inhibitors
  • rac1 GTP-Binding Protein / metabolism


  • Aminoquinolines
  • Anthracenes
  • CCL8 protein, human
  • Chemokine CCL8
  • Chemokine CXCL5
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • NF-kappa B
  • NSC 23766
  • Pyrimidines
  • Tumor Necrosis Factor-alpha
  • pyrazolanthrone
  • Simvastatin
  • JNK Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 9
  • rac1 GTP-Binding Protein