氨基甲基转移酶SMYD2通过调节HDAC3-SRF轴来促进新极端增生
Xiaoxuan Zhong1, Xiang Wei1,2, Yan Xu3
1Division of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Acta pharmaceutica Sinica. B
|February 7, 2024
概括
氨酸甲基转移酶SMYD2通过调节HDAC3-SRF表观遗传轴,促进血管光滑肌肉细胞的增殖和新极度增生. 抑制SMYD2或HDAC3可能为冠心病提供新的治疗策略.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
背景情况:
- 冠状动脉缩,冠状动脉心脏病预后不佳的主要原因,涉及血管光滑肌细胞 (VSMC) 现型切换.
- 在VSMCs和neointimal增生组织中观察到SMYD2表达的升高.
研究的目的:
- 阐明氨基甲基转移酶SMYD2在VSMC表型切换和新极端增生症中的作用.
- 研究涉及SMYD2-HDAC3-SRF轴的潜在表观遗传机制.
主要方法:
- 在VSMC中,SMYD2的过度表达和抑制.
- 使用特定抑制剂 (LLY-507,RGFP966) 抑制SMYD2和HDAC3.
- 在小鼠的动脉损伤模型.
- 转录基因组测序和西方涂抹.
主要成果:
- 过度表达SMYD2有助于VSMC切换和neointima形成;抑制或淘汰SMYD2可以抑制这些过程.
- SMYD2 敲除抑制了血清响应因子 (SRF) 基因;SRF 过度表达逆转了SMYD2 敲除对VSMC增殖的抑制作用.
- SMYD2通过H3K36甲基化促进HDAC3的表达,HDAC3 deacetylatesSRF,增强其活性.
- 抑制HDAC3可以抵消SMYD2诱导的VSMC扩散,并抑制新密度的形成.
结论:
- SMYD2-HDAC3-SRF轴是一个新型表观遗传机制,调节VSMC表型切换和新极端增生.
- 针对这一轴提供了潜在的治疗策略,以预防冠状动脉复缩.
关键词:
在 HDAC3 中,HDAC3 是基斯乙化 基斯乙化希斯甲基化 希斯甲基化这就是LLY-507的目的.形成一个Neointima形成.RGFP96666 是一个关键的产品.这就是SMYD2的原因.通过SRF的乙化.更多相关视频
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