腹主动脉瘤的发病机制尚不清楚。C1q/肿瘤坏死因子相关蛋白家族(CTRPs)是一群新因子。前期，我们在腹主动脉瘤小鼠模型，对4个在心血管系统重要的CTRP亚型(CTRP1/3/6/9)进行了筛查，发现仅CTRP1在血浆和病变血管显著增加。在AngII诱导的腹主动脉瘤模型，发现ApoE-/-;CTRP1-/-(双敲除)小鼠病变较ApoE-/-明显加重，NIK表达增加，非经典NF-κB2通路激活。本项目中，拟在动物、细胞、分子等多个层面，利用ApoE-/-;CTRP1-/-小鼠等，明确CTRP1对腹主动脉瘤进程的影响；研究CTRP1是否经抑制NIK/非经典NF-B2通路调节IL-23/IL-17介导的病变血管慢性炎症；阐明CTRP1调节NIK蛋白的分子机制。项目完成，有望阐明CTRP1在腹主动脉瘤发病中的关键作用，为腹主动脉瘤防治提供新的潜在药物干预靶点。

Abdominal aortic aneurysms (AAA), associated with chronic inflammation of the vascular wall, are extremely dangerous, and ruptured AAA is a dramatic catastrophe. However, the specific pathogenesis for AAA is still unclear. The C1q/TNF-related proteins (CTRPs) are a new family of secreted proteins and play an important role in the body. Previously, we found that CTRP1 was significantly increased in either AAA tissue or plasm in both AAA models (CaCl2-induced C57 mice and AngII-induced ApoE-/- mice), but not for CTRP3/6/9. In AngII-induced AAA model, compared with the ApoE-/-, the ApoE-/-;CTRP1-/- mice showed enlarged AAA diameter, NIK accumulation, NF-κB2 (the non-canonical NF-κB pathway) activation, and increased expression of IL-23 and IL-17. We hypothesize that CTRP1 alleviates AAA development by regulation of chronic inflammation mediated by IL-23/IL-17 through inhibiting NIK/NF-κB2 pathway. AAA models are prepared by ApoE-/- and ApoE-/-;CTRP1-/- mice, macrophages are isolated. This work is designed to investigate: 1) the role of CTRP1 in the progression of AAA; 2) whether CTRP1 retards AAA progression by inhibiting chronic inflammation mediated by IL-23/IL-17 with a manner dependent of NIK/NF-κB2 pathway; 3) the molecular mechanisms for CTRP1 on regulation of NIK expression. Thus, uncovering the pivotal role of CTRP1 in the pathogenesis of AAA, and provide a new strategy and a potential pharmacological target for prevention of AAA.