经皮冠状动脉介入治疗（PCI）是冠心病的主要治疗方法之一，但PCI术后面临支架内再狭窄（ISR）的难题。多数学者认为，血管平滑肌细胞（SMC）由收缩型向合成型转化是ISR的关键。本课题组前期研究发现，YAP参与了SMC表型转化、新生内膜（Neointima）的形成，但机制不明。我们的预实验结果显示，在动脉损伤后，YAP表达上调，NR2F2表达下调；细胞实验表明，YAP负性调控NR2F2的表达，而NR2F2促进了SMC收缩基因的表达。鉴此，我们提出假说：YAP通过抑制NR2F2，促进SMC由收缩型向合成型转化，继而SMC大量增殖分泌，导致Neointima形成。为验证这一假说，本课题将应用SMC特异性敲除YAP小鼠模型及细胞实验，观察敲除YAP对Neointima形成的影响，阐明YAP-NR2F2轴调控SMC表型转化的分子机制，为PCI术后ISR的防治提供新思路。

Percutaneous coronary intervention(PCI）is the most widely performed procedure for the treatment of coronary atherosclerotic heart disease. However, the broad utilization of stents resulted in the new phenomenon of in-stent restenosis (ISR). Most scholars consider that the switch of vascular smooth muscle cells (SMC) from contractile to synthetic phenotype is the most common reason of ISR. Although our previous study showed that Yes-associated protein(YAP) is involved in the switch of SMC phenotype and the neointima formation, the mechanism remains unknown. Our preliminary data showed that YAP expression was induced after arterial injury, while in contrast to upregulated YAP, the expression of NR2F2 was suppressed. In vitro experiments also showed that YAP was negatively correlated with the expression of NR2F2. Moreover, overexpression of NR2F2 promoted the expression of SMC contractile-related genes. Based on these observations, we hypothesize that YAP facilitates the switch of SMC from contractile to synthetic phenotype by suppressing the expression of NR2F2, which leads to the proliferation of SMC and causes the formation of neointima. To test the hypothesis, SMC-specific YAP knockout mice and cell experiments will be used to observe the impact of YAP on the formation of neointima and demonstrate the mechanism of YAP-NR2F2 axis in regulation of SMC phenotypic switch.This research will provide alternative therapeutic strategies for the prevention and the treatment of ISR.