主动脉瘤是多因素诱导具有遗传倾向的致命性心血管疾病。目前主动脉瘤的病理机制尚不明确，缺乏有效的生物力学评估方法。研究发现节段性主动脉僵硬是主动脉瘤形成的重要因素，而TGF-β1介导的主动脉平滑肌细胞的表型转化是主动脉瘤形成的关键环节。.前期研究发现斑点追踪成像技术可评估小鼠节段性主动脉僵硬, 而改变内皮细胞Notch1通路，可增加TGF-β1活性及平滑肌细胞表型从收缩型向分泌型转化，促进主动脉僵硬，提示：主动脉内皮细胞有可能通过Notch-1/TGF-β1信号通路介导平滑肌细胞表型转化，从而诱发主动脉瘤。.为此，本项目拟采用内皮细胞Notch-1条件性基因敲除鼠，基于超声斑点追踪技术综合评估Notch-1敲除对主动脉僵硬及主动脉瘤形成的影响，并结合“主动脉内皮细胞-平滑肌细胞”共培养模型，探讨内皮细胞Notch-1/TGF-β1信号介导平滑肌细胞表型转化在主动脉瘤形成中的作用机制。

Aortic aneurysm is a genetic predisposition fatal cardiovascular disease affected by multiple factors . The pathological mechanism of aortic aneurysm is not clear currently, lacking of effective biomechanical evaluation methods. Segmental aortic stiffness is an important risk for aortic aneurysm and TGF-β1 mediated aortic smooth muscle cells differentiation is a key role in the formation of aortic aneurysm. .Our preliminary data demonstrate important role of speckle tracking imaging in evaluation of segmental aortic stiffness with mice. The conditional Notch-1 deletion of aortic endothelial cells promotes smooth muscle cell phenotype switch through enhanced activity of TGF-β1, and induces aortic stiffness , suggesting that Notch-1/TGF-β1 signal pathway mediated smooth muscle cell phenotype transformation predispose to aortic aneurysm. .We will thoroughly evaluate the effect of Notch-1 in development of aortic stiffness and aortic aneurysm formation based on STI and conditional Notch-1 deletion mice. We will also explore the role of Notch-1/TGF-β1 signaling of endothelial cells mediated smooth muscle cell phenotype switch in promoting aortic aneurysm formation by using coculture model of aortic endothelial cells and smooth muscle cells.