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解析 RNA 甲基化遗传和表观遗传机制在心肌病治疗中的作用。

Unravelling the impact of RNA methylation genetic and epigenetic machinery in the treatment of cardiomyopathy.

机构信息

Department of Cardiology, Affiliated Hospital of Youjiang Medical University for Nationalities, Youjiang Medical University for Nationalities, Baise 533000, China; Laboratory of the Atherosclerosis and Ischemic Cardiovascular Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China.

Graduate School of Youjiang Medical University for Nationalities, Baise 533000, China.

出版信息

Pharmacol Res. 2024 Sep;207:107305. doi: 10.1016/j.phrs.2024.107305. Epub 2024 Jul 11.


DOI:10.1016/j.phrs.2024.107305
PMID:39002868
Abstract

Cardiomyopathy (CM) represents a heterogeneous group of diseases primarily affecting cardiac structure and function, with genetic and epigenetic dysregulation playing a pivotal role in its pathogenesis. Emerging evidence from the burgeoning field of epitranscriptomics has brought to light the significant impact of various RNA modifications, notably N6-methyladenosine (m6A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), N1-methyladenosine (m1A), 2'-O-methylation (Nm), and 6,2'-O-dimethyladenosine (m6Am), on cardiomyocyte function and the broader processes of cardiac and vascular remodelling. These modifications have been shown to influence key pathological mechanisms including mitochondrial dysfunction, oxidative stress, cardiomyocyte apoptosis, inflammation, immune response, and myocardial fibrosis. Importantly, aberrations in the RNA methylation machinery have been observed in human CM cases and animal models, highlighting the critical role of RNA methylating enzymes and their potential as therapeutic targets or biomarkers for CM. This review underscores the necessity for a deeper understanding of RNA methylation processes in the context of CM, to illuminate novel therapeutic avenues and diagnostic tools, thereby addressing a significant gap in the current management strategies for this complex disease.

摘要

心肌病(CM)代表了一组主要影响心脏结构和功能的异质性疾病,遗传和表观遗传失调在其发病机制中起着关键作用。新兴的表观转录组学领域的证据揭示了各种 RNA 修饰的重要影响,特别是 N6-甲基腺苷(m6A)、5-甲基胞嘧啶(m5C)、N7-甲基鸟苷(m7G)、N1-甲基腺苷(m1A)、2'-O-甲基化(Nm)和 6,2'-O-二甲基腺苷(m6Am),对心肌细胞功能和心脏及血管重塑的更广泛过程有重要影响。这些修饰已被证明影响关键的病理机制,包括线粒体功能障碍、氧化应激、心肌细胞凋亡、炎症、免疫反应和心肌纤维化。重要的是,在人类 CM 病例和动物模型中观察到 RNA 甲基化机制的异常,突出了 RNA 甲基化酶的关键作用及其作为 CM 的治疗靶点或生物标志物的潜力。这篇综述强调了在 CM 背景下深入了解 RNA 甲基化过程的必要性,以阐明新的治疗途径和诊断工具,从而解决当前对这种复杂疾病管理策略的重大差距。

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