EZH2 as a novel therapeutic target for atrial fibrosis and atrial fibrillation

Song, Shuai; Zhang, Rui; Mo, Bin‐Feng; Chen, Long; Liu, Liang; Yu, Yi; Cao, Wei; Fang, Guojian; Wan, Yi; Gu, Yue‐ying; Wang, Yuepeng; Li, Yi‐Gang; Yu, Ying; Wang, Qunshan

doi:10.1016/j.yjmcc.2019.08.003

Cited by 52 publications

(61 citation statements)

References 45 publications

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“…These biological processes are important processes involved in the pathophysiological mechanism of AF. Recent research showed that there is a positive correlation between fibrosis and AF, and down-regulation of EZH2 could inhibit Ang-II-induced atrial enlargement and fibrosis and reduce AF vulnerability [ 16 ]. Reactome pathway analysis revealed that the DEGs were associated with the extracellular matrix (ECM) organization and collagen formation.…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes in atrial fibrillation using bioinformatics analysis

Liu

Tang

Zhao

et al. 2020

BMC Cardiovasc Disord

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Background Atrial fibrillation (AF) is one of the most common arrhythmia, which brings huge burden to the individual and the society. However, the mechanism of AF is not clear. This paper aims at screening the key differentially expressed genes (DEGs) of atrial fibrillation and to construct enrichment analysis and protein-protein interaction (PPI) network analysis for these DEGs. Methods The datasets were collected from the Gene Expression Omnibus database to extract data of left atrial appendage (LAA) RNA of patients with or without AF in GSE79768, GSE31821, GSE115574, GSE14975 and GSE41177. Batch normalization, screening of the differential genes and gene ontology analysis were finished by R software. Reactome analysis was used for pathway analysis. STRING platform was utilized for PPI network analysis. At last, we performed reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to validate the expression of key genes in 20 sinus rhythm (SR) LAA tissues and 20 AF LAA tissues. Results A total of 106 DEGs were screened in the merged dataset. Among these DEGs, 74 genes were up-regulated and 32 genes down-regulated. DEGs were mostly enriched in extracellular matrix organization, protein activation cascade and extracellular structure organization. In PPI network, we identified SPP1, COL5A1 and VCAN as key genes which were associated with extracellular matrix. RT-qPCR showed the same expression trend of the three key genes as in our bioinformatics analysis. The expression levels of SPP1, COL5A1 and VCAN were increased in AF tissues compared to SR tissues ( P < 0.05). Conclusion According to the analyses which were conducted by bioinformatics tools, genes related to extracellular matrix were involved in pathology of AF and may become the possible targets for the diagnosis and treatment of AF.

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Section: Discussionmentioning

confidence: 99%

Identification of key genes in atrial fibrillation using bioinformatics analysis

Liu

Tang

Zhao

et al. 2020

BMC Cardiovasc Disord

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“…The method of isolating primary mice atrial fibroblasts is mainly for Song et al, 2019) and was performed as previously described.…”

Section: Methodsmentioning

confidence: 99%

“…At the end of the 16‐week HFD feeding, in vivo cardiac dimensions and functional parameters were assessed by ultrasound instrument (Vivid 7, GE Healthcare). Echocardiography was performed under continuous anesthesia with 2% isoflurane inhalation as previously described (Song et al, 2019). Cardiac parameters included an examination of left atrial diameter (LAD), heart rate (HR), and left ventricle ejection fraction (LVEF).…”

Section: Methodsmentioning

confidence: 99%

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Cadherin‐11 deficiency mitigates high‐fat diet‐induced inflammatory atrial remodeling and vulnerability to atrial fibrillation

Fang

Cao

Chen

et al. 2021

Journal Cellular Physiology

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Atrial fibrillation (AF) is the most common cardiac arrhythmia nowadays. The occurrence of AF is closely associated with obesity. Cadherin‐11 (Cad‐11), as a member of the cadherin family, can make a contribution to diet‐induced obesity and it will be informative to know whether Cad‐11 exerts its effects on atrial remodeling and AF vulnerability in a diet‐induced obesity model. In this study, we demonstrated that the expression of Cad‐11 was significantly upregulated in the left atrium of AF patients with obesity and mice following 16 weeks of high‐fat diet (HFD) feeding. Further confirmed that Cad‐11 could regulate the activity of atrial fibroblasts by participating in inducing proinflammatory cytokines production. At animal levels, we found that although there was a lack of statistical difference in body weight, Cad‐11−/− mice could markedly improve impaired glucose tolerance and hyperlipidemia. Adverse atrial structural remodeling, including atrial enlargement, inflammation, and fibrosis provoked by HFD feeding were mitigated in Cad‐11−/− mice. Mechanistically, Cad‐11 activated mitogen‐activated protein kinases and nuclear factor‐κB for interleukin‐6 production in atrial fibroblasts that may contribute to the atrial fibrosis process in obesity‐related AF, suggesting Cad‐11 might be a new therapeutic target for obesity‐related AF.

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“…Increasing evidence demonstrates that anomalous profiles of histone modifications contribute to the development of diseases such as AF. For instance, patients suffering from AF have increased expression of EZH2, encoding the histone methyltransferase responsible for the H3K27me3 signature, in both atrial cardiomyocytes and fibroblasts [116] . An additional wellknown example applies to histone deacetylases (HDACs) that act as proteostasis regulators in AF, by removing acetyl groups from the lysine residues of nucleosomal histone tails and various non-histone proteins.…”

Section: Histone Modificationsmentioning

confidence: 99%

Functional genomics and epigenomics of atrial fibrillation

Victorino

Alvarez-Franco

Manzanares

2021

Journal of Molecular and Cellular Cardiology

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EZH2 as a novel therapeutic target for atrial fibrosis and atrial fibrillation

Cited by 52 publications

References 45 publications

Identification of key genes in atrial fibrillation using bioinformatics analysis

Identification of key genes in atrial fibrillation using bioinformatics analysis

Cadherin‐11 deficiency mitigates high‐fat diet‐induced inflammatory atrial remodeling and vulnerability to atrial fibrillation

Functional genomics and epigenomics of atrial fibrillation

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