Xu Shuangxiang, Chen Tongyu, Yu Jin, Wan Lei, Zhang Jianjian, Chen Jincao, Wei Wei, Li Xiang
Brain Research Center, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Mol Ther Nucleic Acids. 2024 Jul 19;35(3):102281. doi: 10.1016/j.omtn.2024.102281. eCollection 2024 Sep 10.
Moyamoya disease (MMD) is a progressive steno-occlusive cerebrovascular disorder that predominantly affecting East Asian populations. The intricate interplay of distinct and overlapping mechanisms, including genetic associations such as the RNF213-p.R4810K variant, contributes to the steno-occlusive lesions and moyamoya vessels. However, genetic mutations alone do not fully elucidate the occurrence of MMD, suggesting a potential role for epigenetic factors. Accruing evidence has unveiled the regulatory role of epigenetic markers, including DNA methylation, histone modifications, and non-coding RNAs (ncRNAs), in regulating pivotal cellular and molecular processes implicated in the pathogenesis of MMD by modulating endothelial cells and smooth muscle cells. The profile of these epigenetic markers in cerebral vasculatures and circulation has been determined to identify potential diagnostic biomarkers and therapeutic targets. Furthermore, studies have demonstrated the multifaceted effects of modulating specific epigenetic markers on MMD pathogenesis. These findings hold great potential for the discovery of novel therapeutic targets, translational studies, and clinical applications. In this review, we comprehensively summarize the current understanding of epigenetic mechanisms, including DNA methylation, histone modifications, and ncRNAs, in the context of MMD. Furthermore, we discuss the potential challenges and opportunities that lie ahead in this rapidly evolving field.
烟雾病（MMD）是一种进行性狭窄闭塞性脑血管疾病，主要影响东亚人群。包括RNF213-p.R4810K变异等遗传关联在内的不同机制与重叠机制之间复杂的相互作用，导致了狭窄闭塞性病变和烟雾状血管的形成。然而，仅基因突变并不能完全解释烟雾病的发生，这表明表观遗传因素可能发挥作用。越来越多的证据揭示了表观遗传标记物（包括DNA甲基化、组蛋白修饰和非编码RNA（ncRNA））通过调节内皮细胞和平滑肌细胞，在调控与烟雾病发病机制相关的关键细胞和分子过程中的作用。已经确定了这些表观遗传标记物在脑血管和循环中的特征，以识别潜在的诊断生物标志物和治疗靶点。此外，研究已经证明调节特定表观遗传标记物对烟雾病发病机制具有多方面的影响。这些发现对于发现新的治疗靶点、转化研究和临床应用具有巨大潜力。在本综述中，我们全面总结了目前在烟雾病背景下对表观遗传机制（包括DNA甲基化、组蛋白修饰和ncRNA）的理解。此外，我们还讨论了在这个快速发展的领域中未来潜在的挑战和机遇。
