平滑肌细胞表型转化是胸主动脉瘤发病机制的重要内容，TGF-β通路在维持平滑肌细胞收缩表型中具有重要作用。前期实验发现TGF-β刺激平滑肌细胞诱导miR-494表达，但miR-494的表达积累促进平滑肌细胞向合成型转化；过表达miR-494抑制TGF-β1维持平滑肌细胞合成表型的功能；提示miR-494对TGF-β通路存在反馈调节。基于前期实验的重要发现，我们提出“miR-494/NFAT5/SARA环路反馈抑制TGF-β通路，调节平滑肌细胞表型转化，参与主动脉瘤发病过程”的科学假设。我们拟通过细胞水平明确miR-494/NFAT5/SARA环路内的调控机制，阐明miR-494/NFAT5/SARA环路反馈抑制TGF-β通路，调节平滑肌细胞表型转化的作用机制；在转基因和敲除小鼠模型中，确定miR-494对胸主动脉瘤发病的调节作用。研究结果将为深入理解胸主动脉瘤发病机制提供理论和实验依据。

Smooth muscle cell phenotype is an important part of the pathogenesis of aortic aneurysm, but the molecular mechanism is not clear. TGF-β signaling pathway is closely related to the development of aortic aneurysm. Previous studies have shown that TGF-β stimulates the expression of miR-494, but the effect of miR-494 on the smooth muscle cell phenotype is different, suggesting that miR-494 target gene can feedback to regulate TGF-β signaling pathway. Based on the preliminary work, we present the scientific hypothesis that TGF-β / miR-494 / NFAT5 loop is involved in the pathogenesis of thoracic aortic aneurysm by adjusting the phenotype of smooth muscle cells. We clarified the mechanism of TGF-β / miR-494 / NFAT5 loop on the phenotype transformation of smooth muscle cells by clarifying the molecular mechanism of TGF-β / miR-494 / NFAT5 loop interaction at the cellular level. In transgenic and knockout Mouse model, to determine the TGF-β / miR-494 / NFAT5 loop on the development of thoracic aortic aneurysm regulatory role. The results will provide a theoretical and experimental basis for understanding the pathogenesis of thoracic aortic aneurysm.