Key result
Statins inhibited the Rac1/NF-κB pathway and significantly reduced the secretion of MMP-9, MCP-2, and CXCL5 in human abdominal aortic aneurysm tissues ex vivo.
Why the study?
Do statins inhibit inflammation-related pathways in human abdominal aortic aneurysm tissue?
Do statins inhibit inflammation-related pathways in human abdominal aortic aneurysm tissue?
Statins directly inhibit the Rac1/NF-κB pathway to suppress MMP-9 and chemokine secretion in human AAA tissue, providing a mechanistic basis for their potential to attenuate AAA progression.
Answers are grounded in this paper and cite their sources.
Provides mechanistic support for statins in human AAA; leaves open translation to clinical progression.
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.
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Yoshimura et al. (2015) studied Abdominal aortic aneurysm. Statins (simvastatin, pitavastatin) was evaluated on Activation of NF-κB and secretion of MMP-9, MCP-2, and CXCL5. Statins inhibited the Rac1/NF-κB pathway and significantly reduced the secretion of MMP-9, MCP-2, and CXCL5 in human abdominal aortic aneurysm tissues ex vivo.
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