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-1β, 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.

中文翻译：

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IFI16通过调节caspase-1 /IL-1β/ MCPIP1途径促进腹主动脉瘤的发病

目的

腹主动脉瘤（AAA）是一种多因素进行性血管疾病，其特征在于慢性炎症细胞浸润。我们调查了IFI16和ASC炎性小体在AAA发育和进展中所起的作用。

材料和方法

进行了蛋白质印迹和qRT-PCR研究，以分析AAA标本和小鼠血管平滑肌细胞（VSMC）中相关基因的表达。通过流式细胞仪评估VSMCs的凋亡率和ROS水平。进行Transwell分析以分析VSMC的迁移能力。通过ELISA分析培养的VSMC的上清液中MCP-1，IL-1β和IL-6的水平。

主要发现

在AAA标本和经Ang-II处理的VSMC中发现IFI16表达水平升高。IFI16和ASC沉默抑制了接受Ang-II处理的VSMC的凋亡和迁移能力，减少了对主动脉壁的弹性损伤，并降低了MMP表达水平。MCPIP1过表达逆转了IFI16敲低在Ang-II诱导的VSMC中的作用。

意义

我们的数据表明，IFC16和ASC表达的上调可能会促进VSMC的凋亡，增强炎症反应并通过MCPIP1相关机制损害血管壁弹性。炎性体成分IFI16和ASC可能参与AAA进程，并充当诊断和治疗AAA的靶分子。