Hippo-MST信号通路参与Stanford A型主动脉夹层形成的机制研究

Stanford A型主动脉夹层（STAAD）的死亡率极高,主动脉壁细胞外基质和血管平滑肌(VSMC)的变化在STAAD的发病过程中发挥重要作用。我们前期研究发现:STAAD患者和小鼠STAAD模型形成过程中升主动脉壁的细胞外基质遭到破坏,伴VSMC凋亡增多,Hippo-MST信号通路下游YAP蛋白被磷酸化，活性下降。Hippo-MST通路在STAAD形成中的作用和机制国内外未见报道。本研究通过体内体外结合,从分子、细胞、整体三个水平研究以下科学问题:①临床水平观察Hippo-MST 信号通路在STAAD中的变化②动物模型水平验证其是否参与STAAD形成③Hippo-MST信号通路参与STAAD发生的分子机制。最终为探索STAAD的发病机制、寻找早期诊断与治疗方法提供理论依据。

The mortality of Stanford type A aortic dissection (STAAD) is extremely high. The disorders of aortic wall extracellular matrix and vascular smooth muscle (VSMC) play an important role in the pathogenesis of STAAD. According to our previous study, the extracellular matrix of ascending aorta walls of STAAD patients and in the development of STAAD mouse models were damaged, the apoptosis of VSMC increased, and YAP protein, which was the downstream of Hippo-MST signaling pathway, was phosphorylated and its activity decreased. The role and mechanism of Hippo-MST pathway in the development of STAAD have not been clarified now. In this study, the following scientific questions will be studied on the molecular, cellular and overall levels in vivo and in vitro: ① The changes of Hippo-MST signaling pathway in STAAD will be observed at clinical level; ② The role of Hippo-MST signaling pathway in the development of STAAD will be verified in animal; ③The molecular mechanism of Hippo-MST signaling pathway contributing in the development of STAAD. Finally, it will provide a theoretical basis for exploring the pathogenesis of STAAD and searching for early diagnosis and treatment methods.