Analysis of Genes Involved in Persistent Atrial Fibrillation: Comparisons of ‘Trigger’ and ‘Substrate’ Differences
Background/Aims: Recent research has improved our understanding of the pulmonary vein and surrounding left atrial (LA-PV) junction and the left atrial appendage (LAA), which are considered the ‘trigger’ and ‘substrate’ in the development of atrial fibrillation (AF), respectively. Herein, with the ai...
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2018-06-01
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doaj-8f7dbe49f0ed4c86b983e7021424824e2020-11-25T00:50:24ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-06-014731299130910.1159/000490225490225Analysis of Genes Involved in Persistent Atrial Fibrillation: Comparisons of ‘Trigger’ and ‘Substrate’ DifferencesRongjun ZouMinglei YangWanting ShiChengxi ZhengHui ZengXifeng LinDingwen ZhangSongran YangPing HuaBackground/Aims: Recent research has improved our understanding of the pulmonary vein and surrounding left atrial (LA-PV) junction and the left atrial appendage (LAA), which are considered the ‘trigger’ and ‘substrate’ in the development of atrial fibrillation (AF), respectively. Herein, with the aim of identifying the underlying potential genetic mechanisms, we compared differences in gene expression between LA-PV junction and LAA specimens via bioinformatic analysis. Methods: Microarray data of AF (GSE41177) were downloaded from the Gene Expression Omnibus database. In addition, linear models for microarray data limma powers differential expression analyses and weighted correlation network analysis (WGCNA) were applied. Results: From the differential expression analyses, 152 differentially expressed genes and hub genes, including LEP, FOS, EDN1, NMU, CALB2, TAC1, and PPBP, were identified. Our analysis revealed that the maps of extracellular matrix (ECM)-receptor interactions, PI3K-Akt and Wnt signaling pathways, and ventricular cardiac muscle tissue morphogenesis were significantly enriched. In addition, the WGCNA results showed high correlations between genes and related genetic clusters to external clinical characteristics. Maps of the ECM-receptor interactions, chemokine signaling pathways, and the cell cycle were significantly enriched in the genes of corresponding modules and closely associated with AF duration, left atrial diameter, and left ventricular ejection function, respectively. Similarly, mapping of the TNF signaling pathway indicated significant association with genetic traits of ischemic heart disease, hypertension, and diabetes comorbidity. Conclusions: The ECM-receptor interaction as a possible central node of comparison between LA-PV and LAA samples reflected the special functional roles of ‘triggers’ and ‘substrates’ and may be closely associated with AF duration. Furthermore, LEP, FOS, EDN1, NMU, CALB2, TAC1, and PPBP genes may be implicated in the occurrence and maintenance of AF through their interactions with each other.https://www.karger.com/Article/FullText/490225Bioinformatics analysisAtrial fibrillationPulmonary vein and the surrounding left atrial junctionLeft atrial appendage |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rongjun Zou Minglei Yang Wanting Shi Chengxi Zheng Hui Zeng Xifeng Lin Dingwen Zhang Songran Yang Ping Hua |
spellingShingle |
Rongjun Zou Minglei Yang Wanting Shi Chengxi Zheng Hui Zeng Xifeng Lin Dingwen Zhang Songran Yang Ping Hua Analysis of Genes Involved in Persistent Atrial Fibrillation: Comparisons of ‘Trigger’ and ‘Substrate’ Differences Cellular Physiology and Biochemistry Bioinformatics analysis Atrial fibrillation Pulmonary vein and the surrounding left atrial junction Left atrial appendage |
author_facet |
Rongjun Zou Minglei Yang Wanting Shi Chengxi Zheng Hui Zeng Xifeng Lin Dingwen Zhang Songran Yang Ping Hua |
author_sort |
Rongjun Zou |
title |
Analysis of Genes Involved in Persistent Atrial Fibrillation: Comparisons of ‘Trigger’ and ‘Substrate’ Differences |
title_short |
Analysis of Genes Involved in Persistent Atrial Fibrillation: Comparisons of ‘Trigger’ and ‘Substrate’ Differences |
title_full |
Analysis of Genes Involved in Persistent Atrial Fibrillation: Comparisons of ‘Trigger’ and ‘Substrate’ Differences |
title_fullStr |
Analysis of Genes Involved in Persistent Atrial Fibrillation: Comparisons of ‘Trigger’ and ‘Substrate’ Differences |
title_full_unstemmed |
Analysis of Genes Involved in Persistent Atrial Fibrillation: Comparisons of ‘Trigger’ and ‘Substrate’ Differences |
title_sort |
analysis of genes involved in persistent atrial fibrillation: comparisons of ‘trigger’ and ‘substrate’ differences |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2018-06-01 |
description |
Background/Aims: Recent research has improved our understanding of the pulmonary vein and surrounding left atrial (LA-PV) junction and the left atrial appendage (LAA), which are considered the ‘trigger’ and ‘substrate’ in the development of atrial fibrillation (AF), respectively. Herein, with the aim of identifying the underlying potential genetic mechanisms, we compared differences in gene expression between LA-PV junction and LAA specimens via bioinformatic analysis. Methods: Microarray data of AF (GSE41177) were downloaded from the Gene Expression Omnibus database. In addition, linear models for microarray data limma powers differential expression analyses and weighted correlation network analysis (WGCNA) were applied. Results: From the differential expression analyses, 152 differentially expressed genes and hub genes, including LEP, FOS, EDN1, NMU, CALB2, TAC1, and PPBP, were identified. Our analysis revealed that the maps of extracellular matrix (ECM)-receptor interactions, PI3K-Akt and Wnt signaling pathways, and ventricular cardiac muscle tissue morphogenesis were significantly enriched. In addition, the WGCNA results showed high correlations between genes and related genetic clusters to external clinical characteristics. Maps of the ECM-receptor interactions, chemokine signaling pathways, and the cell cycle were significantly enriched in the genes of corresponding modules and closely associated with AF duration, left atrial diameter, and left ventricular ejection function, respectively. Similarly, mapping of the TNF signaling pathway indicated significant association with genetic traits of ischemic heart disease, hypertension, and diabetes comorbidity. Conclusions: The ECM-receptor interaction as a possible central node of comparison between LA-PV and LAA samples reflected the special functional roles of ‘triggers’ and ‘substrates’ and may be closely associated with AF duration. Furthermore, LEP, FOS, EDN1, NMU, CALB2, TAC1, and PPBP genes may be implicated in the occurrence and maintenance of AF through their interactions with each other. |
topic |
Bioinformatics analysis Atrial fibrillation Pulmonary vein and the surrounding left atrial junction Left atrial appendage |
url |
https://www.karger.com/Article/FullText/490225 |
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