血管平滑肌细胞（VSMC）表型转化在血管再狭窄的发生中起关键作用，但具体机制不完全清楚。我们最近报道了甲基转移酶SMYD2在VSMC表型转化及再狭窄中显著下调；条件性敲除小鼠VSMC中SMYD2促进VSMC表型转化和再狭窄的发生。最新预实验显示，敲除SMYD2下调标志基因启动子CArG区域H3K4甲基化；进一步研究提示SMYD2与共转录因子Myocardin相互结合。本课题拟通过解决“SMYD2是否以及如何通过Myocardin介导CArG区域H3K4甲基化和染色体结构重塑参与VSMC表型转化和再狭窄的发生”这一关键科学问题，进而验证科学假说：再狭窄发生时，VSMC中SMYD2下调，使得被Myocardin募集到CArG区域的SMYD2减少，降低该区域H3K4甲基化，染色体由开放结构变为关闭结构，从而导致VSMC表型转化。本项目有望为临床血管再狭窄的防治提供新靶点。

Vascular smooth muscle cell (VSMC) phenotypic switch plays a key role in the occurrence of vascular restenosis. However, the molecular mechanism is still unclear. We recently reported that methyltransferase SMYD2 was significantly down-regulated in VSMC phenotypic switch and vascular restenosis. Conditional VSMC SMYD2 knockout in mice promoted VSMC phenotypic switch and vascular restenosis. Our latest results showed that deletion of SMYD2 down-regulated the H3K4 methylation level in the CArG region of the VSMC marker gene promoter. Further research suggested that SMYD2 may bind to the co-transcription factor Myocardin. This study intends to answer the following scientific question that Whether and how SMYD2 mediates H3K4 methylation and chromosomal structure remodeling in CArG region through Myocardin to participate in VSMC phenotypic transition and vascular restenosis. Our scientific hypothesis is that when restenosis occurs, SMYD2 is down-regulated in VSMC, which reduces the SMYD2 in the CArG region recruited by Myocardin, inhibits the H3K4 methylation in this region, and the chromosome changes from an open structure to a closed structure, resulting in VSMC phenotypic switch. This project is expected to provide new targets for the prevention and treatment of vascular restenosis.