IFI16 contributes to the pathogenesis of abdominal aortic aneurysm by regulating the caspase-1/IL-1β/MCPIP1 pathway

Aims: Abdominal aortic aneurysm (AAA) is a multi-factorial progressive vascular disease characterized by chronic inflammatory cell infiltration. We investigated the roles played by IFI16 and ASC inflammasomes in AAA development and progression. Materials and methods: Western blot and qRT-PCR studies were performed to analyze the expression of relative genes in AAA specimens and mouse vascular smooth muscle cells (VSMCs). The apoptosis rates and ROS levels of VSMCs were assessed by flow cytometry. Transwell assays were performed to analyze the migration ability of VSMCs. The levels of MCP-1, IL-1 beta, and IL-6 in the supernatants of cultured VSMCs were analyzed by ELISA. Key findings: Increased levels of IFI16 expression were found in AAA specimens and Ang-II-treated VSMCs. IFI16 and ASC silencing suppressed the apoptosis and migration ability of VSMCs undergoing Ang-II treatment, reduced elasticity damage to the aortic wall, and decreased the levels of MMP expression. The effect of IFI16 knockdown in Ang-II-induced VSMCs was reversed by MCPIP1 overexpression. Significance: Our data suggest that an up-regulation of IFI16 and ASC expression might promote the apoptosis of VSMCs, enhance the inflammatory response, and impairs vascular wall elasticity via a MCPIP1-related mechanism. The inflammasome components IFI16 and ASC might be involved in AAA progression and serve as target molecules for diagnosing and treating AAA.

Automated summary

Increased expression of IFI16 was found in AAA specimens and Ang-II-treated VSMCs. Silencing IFI16 and ASC suppressed apoptosis and migration ability of VSMCs, reduced elasticity damage and MMP expression. Thus, IFI16 and ASC may play important roles in the progression of AAA.