组蛋白三甲基化修饰调控血管内皮功能在动脉粥样硬化中的作用及机制研究

Epigenetic modification plays an important role in the development and progression of atherosclerosis, and histone methylation is thought to be the major regulatory mechanism. Our preliminary research showed that the level of histone tri-methylation modification was significantly higher in human atherosclerotic vascular endothelial cells than in human normal controls. However, the role of histone methylation in the development and progression of atherosclerosis remains poorly understood. The present study aims to explore the regulatory mechanism of histone tri-methylation in human atherosclerotic vascular endothelial cells. In Part I, the status of histone tri-methylation modifications in human atherosclerotic coronary artery will be assessed by immunohistochemical and western blot methods. In part II, major target genes for histone tri-methylation modifications in human atherosclerotic vascular endothelium will be detected using ChIP-Seq technique,and the possible patterns of regulation will be characterized. In Part III, the results of the Part II will be verified in vitro and in vivo, to further explore regulatory mechanism of histone tri-methylation in the development and progression of atherosclerosis. The genes will be mapped. Overall, this study investigates the pathogenesis of atherosclerosis from a new viewpoint of histone tri-methylation modifications, which may provide new targets and ideas for the treatment of atherosclerosis.

表观遗传修饰在动脉粥样硬化的发生过程中起重要作用,而组蛋白甲基化修饰是其主要调控方式。本课题组前期研究发现，人动脉粥样硬化血管内皮细胞组蛋白三甲基化修饰水平显著高于人正常血管内皮细胞。至今，对组蛋白甲基化修饰在人动脉粥样硬化发生中的调控机制仍知之甚少。本课题旨在探讨组蛋白三甲基化修饰调控血管内皮功能在人动脉粥样硬化发生中的作用和机理，包括：（1）检测人动脉粥样硬化血管中组蛋白三甲基化修饰状态。（2）用ChIP-Seq方法寻找组蛋白三甲基化修饰调控血管内皮在人动脉粥样硬化发生中相关基因。（3）体内外实验验证ChIP-Seq结果，进一步探讨组蛋白三甲基化修饰调控血管内皮细胞在人动脉粥样硬化发生发展中的作用机制。本研究从组蛋白三甲基化修饰这个新视点出发，探讨它在动脉粥样硬化发生中对血管内皮的作用，以期为动脉粥样硬化的治疗提供新的靶点和思路。

表观遗传修饰在动脉粥样硬化的发生过程中起重要作用,而组蛋白甲基化修饰是其主要调控方式。本课题组前期研究发现，人动脉粥样硬化血管内皮细胞组蛋白三甲基化修饰水平显著高于人正常血管内皮细胞。至今，对组蛋白甲基化修饰在人动脉粥样硬化发生中的调控机制仍知之甚少。本课题旨在探讨组蛋白三甲基化修饰调控血管内皮功能在人动脉粥样硬化发生中的作用和机理，本研究检测了人动脉粥样硬化血管中组蛋白三甲基化修饰状态，并用ChIP-Seq和生物信息学方法找到组蛋白三甲基化修饰调控血管内皮在人动脉粥样硬化发生中相关基因（MT1E等），绘制相关的调控网络图，体内外实验验证ChIP-Seq结果，进一步探明了组蛋白三甲基化修饰调控血管内皮细胞在人动脉粥样硬化发生发展中的作用机制。本研究从组蛋白三甲基化修饰这个新视点出发，探讨它在动脉粥样硬化发生中对血管内皮的作用，从而为动脉粥样硬化的治疗提供新的靶点和思路。