Chen Yanjun, Liang Lingli, Wu Chunyan, Cao Zitong, Xia Linzhen, Meng Jun, Wang Zuo
Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, China.
The Third Affiliated Hospital of University of South China, Hengyang, China.
DNA Cell Biol. 2022 Sep;41(9):824-837. doi: 10.1089/dna.2022.0278. Epub 2022 Jul 27.
Atherosclerosis is a complex vascular inflammatory disease in which multiple cell types are involved, including vascular smooth muscle cells (VSMCs). In response to vascular injury and inflammatory stimuli, VSMCs undergo a "phenotypic switching" characterized by extracellular matrix secretion, loss of contractility, and abnormal proliferation and migration, which play a key role in the progression of atherosclerosis. DNA methylation modification is an important epigenetic mechanism that plays an important role in atherosclerosis. Studies investigating abnormal DNA methylation in patients with atherosclerosis have determined a specific DNA methylation profile, and proposed multiple pathways and genes involved in the etiopathogenesis of atherosclerosis. Recent studies have also revealed that DNA methylation modification controls VSMC function by regulating gene expression involved in atherosclerosis. In this review, we summarize the recent advances regarding the epigenetic control of VSMC function by DNA methylation in atherosclerosis and provide insights into the development of VSMC-centered therapeutic strategies.
动脉粥样硬化是一种复杂的血管炎症性疾病,涉及多种细胞类型,包括血管平滑肌细胞(VSMC)。响应血管损伤和炎症刺激,VSMC经历“表型转换”,其特征为细胞外基质分泌、收缩力丧失以及异常增殖和迁移,这些在动脉粥样硬化进展中起关键作用。DNA甲基化修饰是一种重要的表观遗传机制,在动脉粥样硬化中发挥重要作用。对动脉粥样硬化患者异常DNA甲基化的研究确定了特定的DNA甲基化谱,并提出了多个参与动脉粥样硬化发病机制的途径和基因。最近的研究还表明,DNA甲基化修饰通过调节参与动脉粥样硬化的基因表达来控制VSMC功能。在本综述中,我们总结了动脉粥样硬化中DNA甲基化对VSMC功能进行表观遗传控制的最新进展,并为以VSMC为中心的治疗策略的开发提供见解。