血管平滑肌细胞（VSMC）表型转化（收缩型向分泌型转化）在腹主动脉瘤（AAA）的形成中起关键作用，但具体机制不完全清楚。我们观察到，在人和鼠AAA组织中, VSMC富集的环状RNA circSmad4显著低表达，沉默其促进VSMC表型转化。进一步预实验显示，circSmad4直接结合去分化转录抑制因子MSX1并抑制msx1基因转录和蛋白表达；过表达MSX1促进circSmad4向胞核转移；生物信息学预测msx1基因启动子含有circSmad4结合序列。因此，本项目拟通过解决“circSmad4是否以及如何通过MSX1参与VSMC表型转化和AAA形成”这一科学问题，来验证我们的科学假说：AAA发生时，VSMC的circSmad4下调，其跟随蛋白MSX1入核减少，引领MSX1结合到自身启动子的作用弱化，减弱基因msx1自我转录抑制，从而导致VSMC表型转化。本项目有望为AAA的防治提供新靶点。

Vascular smooth muscle cell (VSMC) phenotypic transition, VSMC morphologic and function transition from a quiescent contractile phenotype to synthetic phenotype, plays a key role in abdominal aortic aneurysm (AAA) formation and progression. However, the molecular mechanism is still unclear. We found that the expression of circSmad4, a circular RNA enriched in VSMC, was significantly downregulated in human and animal AAA tissues, and that circSmad4 knockdown promoted VSMC phenotypic transition. In further preliminary experiment, it is found that circSmad4 binded directly to MSX1, a dedifferentiating transcription inhibitor and inhibited the protein and mRNA expression of msx1 gene, and that the nuclear accumulation of circSmad4 was enhanced by overexpression of MSX1. Bioinformatics predicts circSmad4 binding sequence in msx1 promoter. Therefore, this project intends to clarify the scientific question that whether and how circSmad4 participate in VSMC phenotypic transition and AAA formation by regulating MSX1. We speculate that the reduction of circSmad4 binding to MSX1 and its following entrance into the nucleus due to the down-regulation of circSmad4 expression in VSMC, would weaken the effect of circSmad4 guiding MSX1 to bind to msx1 gene promoter, thus attenuating the transcriptional autorepression of msx1 and then facilitating VSMC phenotypic transition during AAA formation. The project will provide a new target for AAA prevention and treatment in the future.