Differential left-to-right atria gene expression ratio in human sinus rhythm and atrial fibrillation: Implications for arrhythmogenesis and thrombogenesis

Tsai, Feng Chun; Lin, Ying‐Li; Chang, Shang Hung; Chang, Gwo‐Jyh; Hsu, Yi-Chih; Lin, Yu‐Chi; Lee, Yun Shien; Wang, Chun Li; Yeh, Yu Min

doi:10.1016/j.ijcard.2016.07.103

Cited by 49 publications

(45 citation statements)

References 38 publications

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“…In recent years, the number of genes identified by GWAS to be associated with AF has increased from 30 to around 212 potential genes ( Supplementary Table S6) (2,10,14,19,21,26,30,31,34,38,43). Seven of these potential genes were found to be differentially expressed in this edgeR data set.…”

Section: Discussionmentioning

confidence: 93%

Differentially expressed genes for atrial fibrillation identified by RNA sequencing from paired human left and right atrial appendages

Thomas

Cabrera

Finlay

et al. 2019

Physiological Genomics

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Atrial fibrillation is a significant worldwide contributor to cardiovascular morbidity and mortality. Few studies have investigated the differences in gene expression between the left and right atrial appendages, leaving their characterization largely unexplored. In this study, differential gene expression was investigated in atrial fibrillation and sinus rhythm using left and right atrial appendages from the same patients. RNA sequencing was performed on the left and right atrial appendages from five sinus rhythm (SR) control patients and five permanent AF case patients. Differential gene expression in both the left and right atrial appendages was analyzed using the Bioconductor package edgeR. A selection of differentially expressed genes, with relevance to atrial fibrillation, were further validated using quantitative RT-PCR. The distribution of the samples assessed through principal component analysis showed distinct grouping between left and right atrial appendages and between SR controls and AF cases. Overall 157 differentially expressed genes were identified to be downregulated and 90 genes upregulated in AF. Pathway enrichment analysis indicated a greater involvement of left atrial genes in the Wnt signaling pathway whereas right atrial genes were involved in clathrin-coated vesicle and collagen formation. The differing expression of genes in both left and right atrial appendages indicate that there are different mechanisms for development, support and remodeling of AF within the left and right atria.

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Section: Discussionmentioning

confidence: 93%

Differentially expressed genes for atrial fibrillation identified by RNA sequencing from paired human left and right atrial appendages

Thomas

Cabrera

Finlay

et al. 2019

Physiological Genomics

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“…4A and B. As previous studies demonstrated that differential left-to-right atria gene expression ratio may affect arrhythmogenesis and thrombogenesis of AF (14), which may suggest a specific co-expression pattern, the blue module was analyzed further as it exhibited a significant and relatively substantial correlation with both the LA (r=0.53; P=0.006) and AF (r=-0.49; P=0.01). Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The original study involving this dataset, conducted by Tsai et al (14), revealed the differences between LA-to-RA transcriptional profiles between AF and SR, and suggested that AF was associated with differential LA-to-RA gene expression, which was related to specific ion channels and pathways, as well as upregulation of thrombogenesis-associated genes in the LA appendage. The major differences in the genes or modules obtained in the present study, compared with the results from the study by Tsai et al (14) was that the present study used a more comprehensive method, WGCNA, not only identifying the blue module as an important regulatory module of AF with increased specificity in the LA associated with complement, coagulation and extracellular matrix formation, expanding upon their results in LA-to-RA DEGs associated-pathways, but also identifying 2 critical modules for AF: The green module, which was associated with energy metabolism; and the magenta module, which was associated with multiple interactive pathways associated with apoptosis and inflammation. The in-depth analyses performed in the present and the results obtained cannot be obtained from conventional microarray DEGs analyses.…”

Section: Discussionmentioning

confidence: 96%

“…The dataset contains data from 13 pairs of left and right atrial appendages from 7 patients with persistent AF and 6 patients with SR (14). The dataset consisted of patients with AF whom presented with persistent AF for >6 months, or patients with SR with no evidence of AF and whom did not use any anti-arrhythmic drugs (14). The characteristics of the patients are summarized in Table SI, which may be downloaded from GEO (ncbi.nlm.nih.gov/geo/).…”

Section: Methodsmentioning

confidence: 99%

“…The GSE79768 dataset was used in the present study, which contained 26 samples from paired left atria (LA) and right atria (RA) in patients with persistent AF or sinus rhythm (SR) (14). Two key modules with the highest level of significance correlation with AF were identified, and the 3 genes with the highest intramodular connectivity were selected as the hub genes in the respective modules for AF.…”

Section: Introductionmentioning

confidence: 99%

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Weighted gene co‑expression network analysis to identify key modules and hub genes associated with atrial fibrillation

Wang

et al. 2019

Int J Mol Med

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Atrial fibrillation (AF) is the most common form of cardiac arrhythmia and significantly increases the risks of morbidity, mortality and health care expenditure; however, treatment for AF remains unsatisfactory due to the complicated and incompletely understood underlying mechanisms. In the present study, weighted gene co-expression network analysis (WGCNA) was conducted to identify key modules and hub genes to determine their potential associations with AF. WGCNA was performed in an AF dataset GSE79768 obtained from the Gene Expression Omnibus, which contained data from paired left and right atria in cardiac patients with persistent AF or sinus rhythm. Differentially expressed gene (DEG) analysis was used to supplement and validate the results of WGCNA. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were also performed. Green and magenta modules were identified as the most critical modules associated with AF, from which 6 hub genes, acetyl-CoA Acetyltransferase 1, death domain-containing protein CRADD, gypsy retrotransposon integrase 1, FTX transcript, XIST regulator, transcription elongation factor A like 2 and minichromosome maintenance complex component 3 associated protein, were hypothesized to serve key roles in the pathophysiology of AF due to their increased intramodular connectivity. Functional enrichment analysis results demonstrated that the green module was associated with energy metabolism, and the magenta module may be associated with the Hippo pathway and contain multiple interactive pathways associated with apoptosis and inflammation. In addition, the blue module was identified to be an important regulatory module in AF with a higher specificity for the left atria, the genes of which were primarily correlated with complement, coagulation and extracellular matrix formation. These results suggest that may improve understanding of the underlying mechanisms of AF, and assist in identifying biomarkers and potential therapeutic targets for treating patients with AF.

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Epigenetic regulation of cardiac electrophysiology in atrial fibrillation: HDAC2 determines action potential duration and suppresses NRSF in cardiomyocytes

et al. 2021

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Differential left-to-right atria gene expression ratio in human sinus rhythm and atrial fibrillation: Implications for arrhythmogenesis and thrombogenesis

Cited by 49 publications

References 38 publications

Differentially expressed genes for atrial fibrillation identified by RNA sequencing from paired human left and right atrial appendages

Differentially expressed genes for atrial fibrillation identified by RNA sequencing from paired human left and right atrial appendages

Weighted gene co‑expression network analysis to identify key modules and hub genes associated with atrial fibrillation

Epigenetic regulation of cardiac electrophysiology in atrial fibrillation: HDAC2 determines action potential duration and suppresses NRSF in cardiomyocytes

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