研究证实，血管紧张素II（AngII）通路是主动脉夹层的重要致病机制，也是治疗主动脉夹层的突破口。但目前干预AngII治疗 TGF-β通路异常的主动脉夹层理论存在悖论。我们的前期研究发现：1.降低的TGF-β通路与升高的AngII通路之间存在某种协同关系，导致主动脉夹层进展；2.其机制可能与RGS2表达增高相关；3.抑制SMAD3磷酸化，增加RGS2蛋白表达。我们推测，RGS2蛋白高表达导致主动脉中层平滑肌基础张力降低，在压力应激下MAPK途径过度激活、病变局部T细胞过度活化，促进主动脉夹层发生。本课题将：1.建立RGS2平滑肌细胞/T细胞特异性敲除小鼠主动脉夹层模型，研究不同细胞组分RGS2敲除后对主动脉夹层的保护效应及机制；2.阐明SMAD3对RGS2的调控机制，证明TGF-β通路与AngII通路之间的相互作用。本课题为完善主动脉夹层发病机制，探讨可能的治疗靶点和思路提供实验依据。

Angiotensin II is implicated in the development of aortic aneurysm and dissection. Thus, AngII is considered as breakthrough in treatment of aortic dissection. However, there was a paradox in aortic dissection about TGF-β abnormal treatment by AngII. In our previous research we found: 1. Down-regulated TGF-β signaling added up-regulated AngII signaling have synergistic effect, which exacerbate aortic dissection. 2. The possible mechanism is increase RGS2. 3. Inhibition p-SMAD3 could increase RGS2 expression. We hypothesized that high-level RGS2 lead basal tension decreases in VSMC. And stress of blood pressure result in MAPK pathway and T cell over-activation, which accelerate aortic dissection. In this project, we will:1. Using VSMC/T cell specifically RGS2 knockout mice to establish the aortic dissection model, study the effect and mechanism after RGS2 knockout in different cells; 2. To elucidate the regulation of SMAD3 to RGS2 expression, certify the interaction between TGF-β signaling and AngII signaling pathway. This project will improve the pathogenesis of aortic dissection, and provide experimental evidence of new therapeutic target or strategy.