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Epigenetic role of N6-methyladenosine (m6A) RNA methylation in the cardiovascular system

N6-甲基腺苷(m6A)RNA 甲基化在心血管系统的表观遗传学作用

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Abstract

As the most prevalent and abundant transcriptional modification in the eukaryotic genome, the continuous and dynamic regulation of N6-methyladenosine (m6A) has been shown to play a vital role in physiological and pathological processes of cardiovascular diseases (CVDs), such as ischemic heart failure (HF), myocardial hypertrophy, myocardial infarction (MI), and cardiomyogenesis. Regulation is achieved by modulating the expression of m6A enzymes and their downstream cardiac genes. In addition, this process has a major impact on different aspects of internal biological metabolism and several other external environmental effects associated with the development of CVDs. However, the exact molecular mechanism of m6A epigenetic regulation has not been fully elucidated. In this review, we outline recent advances and discuss potential therapeutic strategies for managing m6A in relation to several common CVD-related metabolic disorders and external environmental factors. Note that an appropriate understanding of the biological function of m6A in the cardiovascular system will pave the way towards exploring the mechanisms responsible for the development of other CVDs and their associated symptoms. Finally, it can provide new insights for the development of novel therapeutic agents for use in clinical practice.

概 要

作为真核生物基因组中最普遍和最丰富的转录修饰, N6-甲基腺苷(m6A)持续而动态性的调节在缺血性心力衰竭、 心肌肥大和心肌梗死等心血管系统疾病的生理和病理过程中发挥着重要作用. 此外, m6A RNA 甲基化通过改变多种 m6A 酶及下游靶基因的表达, 对与心血管系统疾病发生发展相关的内在生物代谢和外在环境因素起着重要的调节作用. 但是, 目前仍不清楚 m6A 表观遗传调节具体的分子生物学机制. 在此, 我们概述了 m6A RNA 甲基化最新的研究进展及其在常见心血管系统疾病和心血管相关代谢紊乱病理发展中的作用.这将有助于我们正确了解 m6A 在心血管系统中的生物学作用, 并为进一步探索心血管疾病及其相关临床症状的发生机制和开发临床治疗药物, 提供新的理论依据和思路.

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Contributions

Kun ZHAO wrote and edited the manuscript. Chuan-xi YANG and Peng LI collated the literature. Wei SUN edited and revised the manuscript. Kun ZHAO and Xiang-qing KONG designed the study. All authors have read and approved the final manuscript and, therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.

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Correspondence to Xiang-qing Kong.

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Kun ZHAO, Chuan-xi YANG, Peng LI, Wei SUN, and Xiang-qing KONG declare that they have no conflict of interest.

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Project supported by the Grants-in-Aid from the Graduate Research and Innovation Projects of Jiangsu Province (No. KYCX181461), China

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Zhao, K., Yang, Cx., Li, P. et al. Epigenetic role of N6-methyladenosine (m6A) RNA methylation in the cardiovascular system. J. Zhejiang Univ. Sci. B 21, 509–523 (2020). https://doi.org/10.1631/jzus.B1900680

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  • DOI: https://doi.org/10.1631/jzus.B1900680

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