腹主动脉瘤（AAA）的形成跟瘤壁炎症反应和细胞外基质重构紧密相关，但其机制仍未阐明。在前期研究中，申请人发现凝血酶敏感蛋白（TSP）和AAA形成相关，并证实TSP1通过调控瘤壁炎症反应促AAA形成；继续研究发现瘤壁中TSP1和TSP2表达具有时间续贯性，而TSP2能抑制AAA形成。蛋白功能域分析提示TSP1和TSP2大部分功能域相同，但对TGF-β和MMP功能相反。因此申请人推测TSP1/TSP2失衡促进了AAA的形成。本课题拟通过人体组织、体外细胞和动物模型，（1）分析TSP1/TSP2在AAA瘤壁组织和血清中的临床意义，（2）分析并明确TSP1/TSP2调控AAA瘤壁炎症反应中的效应细胞；（3）分析阐明AAA瘤壁中TSP1/TSP2对TGF-β信号通路和细胞外基质重构的作用。本研究对揭示AAA瘤壁炎症反应和细胞外基质重构的机理具有重要意义，为后期探索AAA治疗靶点奠定基础。

Abdominal Aortic Aneurysm (AAA) results from Inflammation and extracellular matrix remodeling of arterial wall. However, the pathological mechanism still remains unclear. In the previous work, we found that the Thrombospondin (TSP) promotes AAA formation by regulating the AAA inflammatory response. We also found there is correlation between TSP1 and TSP2 expression and TSP2 prevents mouse AAA formation. Protein functional domain analysis showed that most functional sites of TSP1 and TSP2 are similar, except the TGF- beta and MMP. Therefore, we put forward the hypothesis that the TSP1 and TSP2 imbalance could promote the formation and development of AAA by influencing the inflammatory response and remodeling of the extracellular matrix. We plan to analyze the expression of TSP1 and TSP2 in the AAA. Then we will analyze and clarify the mechanism of TSP1/TSP2 regulating the inflammation, TGF beta signal pathway and extracellular matrix remodeling of the AAA in vivo and in vitro. The study results might contribute to reveal the mechanism of inflammation and extracellular matrix remodeling in AAA, and explore novel molecular therapeutic targets for treatment of AAA.