gene suppresses intracranial aneurysm formation and rupture through inhibiting the NF-κB signaling pathway mediated inflammatory response.

Intracranial aneurysm (IA) is a critical acquired cerebrovascular disease that may cause subarachnoid hemorrhage, and nuclear factor-κB (NF-κB)-mediated inflammation is involved in the pathogenesis of IA. Adenomatous polyposis coli () gene is a tumor suppressor gene associated with both familial and sporadic cancer. Herein, the purpose of our study is to validate effect of Apc gene on IA formation and rupture by regulating the NF-κB signaling pathway mediated inflammatory response. We collected IA specimens (from incarceration of IA) and normal cerebral arteries (from surgery of traumatic brain injury) to examine expression of Apc and the NF-κB signaling pathway related factors (NF-κB p65 and IκBα). ELISA was used to determine levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β (IL-1β), and IL-6. IA model was established in rats, and Apc-siRNA was treated to verify effect of Apc on IA formation and rupture. Next, regulation of Apc on the NF-κB signaling pathway was investigated. Reduced expression of Apc and IκBα, and increased expression of NF-κB p65 were found in IA tissues. MCP-1, TNF-α, IL-1β, and IL-6 exhibited higher levels in unruptured and ruptured IA, which suggested facilitated inflammatory responses. In addition, the IA rats injected with Apc-siRNA showed further enhanced activation of NF-κB signaling pathway, and up-regulated levels of MCP-1, TNF-α, IL-1β, IL-6, MMP-2, and MMP-9 as well as extent of p65 phosphorylation in IA. Above all, Apc has the potential role to attenuate IA formation and rupture by inhibiting inflammatory response through repressing the activation of the NF-κB signaling pathway.