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Epigenetic signatures in cardiac fibrosis, special emphasis on DNA methylation and histone modification

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Abstract

Cardiac fibrosis is defined as excess deposition of extracellular matrix (ECM), resulting in tissue scarring and organ dysfunction. In recent years, despite the underlying mechanisms of cardiac fibrosis are still unknown, numerous studies suggest that epigenetic regulation of cardiac fibrosis. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix protein, a process the epigenetic machinery plays a pivotal role. Epigenetic modifications contain three main processes: DNA methylation, histone modifications, and noncoding RNAs. Here, we review recent studies that have illustrated key roles for epigenetic events in the control of pro-fibrotic gene expression, and highlight the potential of molecule mechanisms that target epigenetic regulators as a means of treating cardiac fibrosis.

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Abbreviations

miRs:

MicroRNAs

LncRNA:

Long noncoding RNA

ncRNAs:

Noncoding RNAs

α-SMA:

α-smooth muscle actin

ECM:

Extracellular matrix

RNAi:

RNA interference

DNMTs:

DNA methyltransferases

HAT:

Histone acetyl transferase

HDAC:

Histone deacetylase

HCM:

Hypertrophic cardiomyopathy

DBcAMP:

cAMP analog N(6),2’-O-dibutyryladenosine 3′,5′-cyclic monophosphate

MeCP2:

Methyl CpG binding protein 2

CpG:

CpG island

RASAL1:

RAS protein activator like-1

Ras-GTP:

RAS GTPase activating protein

MI:

Myocardial infarction

RAAS:

Renin-angiotensin-aldosterone system

MMP:

Maladjustment of matrix metalloproteinases

EMT:

Epithelial mesenchymal transition

TGF-β:

Transforming growth factor beta

DUSP5:

Dual-specificity phosphatase 5

SHR:

Spontaneously hypertensive rat

EndMT:

Endothelial mesenchymal transition

RASSF1A:

Ras association domain family 1 isoform A

TET:

Ten eleven translocation

TSA:

Trichostatin A

VPA:

Valproic acid

MR:

Mineralocorticoid receptor

MRTF-A:

Myocardin-related transcription factor A

Ang II:

Angiotensin II

EZH1:

Enhancer of zeste homolog 1

TFIID:

Transcription factor II D

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Acknowledgements

This project was supported by the National Natural Science Foundation of China (81700212, 81570295) and Natural Science Foundation of Anhui Provincial Education Department (KJ2017A168).

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  1. Zheng-Yu Song contributed equally to this work.

Authors and Affiliations

  1. School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, Jiangsu Province, China

    Hui Tao, Zheng-Yu Song & Xuan-Sheng Ding

  2. Department of Cardiothoracic Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, Jiangsu Province, China

    Hui Tao & Kai-Hu Shi

  3. Department of Pharmacology, The Second Hospital of Anhui Medical University, Hefei, 230601, China

    Jing-Jing Yang

  4. School of pharmacy, Anhui Medical University, Hefei, 230032, China

    Jun Li

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  1. Hui Tao
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Tao, H., Song, ZY., Ding, XS. et al. Epigenetic signatures in cardiac fibrosis, special emphasis on DNA methylation and histone modification. Heart Fail Rev 23, 789–799 (2018). https://doi.org/10.1007/s10741-018-9694-z

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