Metabolomic and Proteomic Analyses of Persistent Valvular Atrial Fibrillation and Non-Valvular Atrial Fibrillation

Atrial fibrillation (AF) is an abnormal heart rhythm related to an increased risk of heart failure, dementia, and stroke. The distinction between valvular and non-valvular AF remains a debate. In this study, proteomics and metabolomics were integrated to describe the dysregulated metabolites and pro...

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Autores principales: Bo Hu, Wen Ge, Yuliang Wang, Xiaobin Zhang, Tao Li, Hui Cui, Yongjun Qian, Yangyang Zhang, Zhi Li
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:bcfeeb6b48d44ea3888898f22e277c492021-12-01T18:28:59ZMetabolomic and Proteomic Analyses of Persistent Valvular Atrial Fibrillation and Non-Valvular Atrial Fibrillation1664-802110.3389/fgene.2021.789485https://doaj.org/article/bcfeeb6b48d44ea3888898f22e277c492021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.789485/fullhttps://doaj.org/toc/1664-8021Atrial fibrillation (AF) is an abnormal heart rhythm related to an increased risk of heart failure, dementia, and stroke. The distinction between valvular and non-valvular AF remains a debate. In this study, proteomics and metabolomics were integrated to describe the dysregulated metabolites and proteins of AF patients relative to sinus rhythm (SR) patients. Totally 47 up-regulated and 41 down-regulated proteins in valvular AF, and 59 up-regulated and 149 down-regulated proteins in non-valvular AF were recognized in comparison to SR patients. Moreover, 58 up-regulated and 49 significantly down-regulated metabolites in valvular AF, and 47 up-regulated and 122 down-regulated metabolites in persistent non-valvular AF patients were identified in comparison to SR patients. Based on analysis of differential levels of metabolites and proteins, 15 up-regulated and 22 down-regulated proteins, and 13 up-regulated and 122 down-regulated metabolites in persistent non-valvular AF were identified relative to valvular AF. KEGG pathway enrichment analysis showed the altered proteins and metabolites were significantly related to multiple metabolic pathways, such as Glycolysis/Gluconeogenesis. Interestingly, the enrichment pathways related to non-valvular AF were obviously different from those in valvular AF. For example, valvular AF was significantly related to Glycolysis/Gluconeogenesis, but non-valvular AF was more related to Citrate cycle (TCA cycle). Correlation analysis between the differentially expressed proteins and metabolites was also performed. Several hub proteins with metabolites were identified in valvular AF and non-valvular AF. For example, Taurine, D-Threitol, L-Rhamnose, and DL-lactate played crucial roles in valvular AF, while Glycerol-3-phosphate dehydrogenase, Inorganic pyrophosphatase 2, Hydroxymethylglutaryl-CoAlyase, and Deoxyuridine 5-triphosphate nucleotidohydrolase were crucial in non-valvular AF. Then two hub networks were recognized as potential biomarkers, which can effectively distinguish valvular AF and non-valvular persistent AF from SR samples, with areas under curve of 0.75 and 0.707, respectively. Hence, these metabolites and proteins can be used as potential clinical molecular markers to discriminate two types of AF from SR samples. In summary, this study provides novel insights to understanding the mechanisms of AF progression and identifying novel biomarkers for prognosis of non-valvular AF and valvular AF by using metabolomics and proteomics analyses.Bo HuWen GeYuliang WangXiaobin ZhangTao LiHui CuiYongjun QianYangyang ZhangZhi LiFrontiers Media S.A.articlemetabolicproteomicvalvular atrial fibrillationnon-valvular atrial fibrillationpersistent atrial fibrillationGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic metabolic
proteomic
valvular atrial fibrillation
non-valvular atrial fibrillation
persistent atrial fibrillation
Genetics
QH426-470
spellingShingle metabolic
proteomic
valvular atrial fibrillation
non-valvular atrial fibrillation
persistent atrial fibrillation
Genetics
QH426-470
Bo Hu
Wen Ge
Yuliang Wang
Xiaobin Zhang
Tao Li
Hui Cui
Yongjun Qian
Yangyang Zhang
Zhi Li
Metabolomic and Proteomic Analyses of Persistent Valvular Atrial Fibrillation and Non-Valvular Atrial Fibrillation
description Atrial fibrillation (AF) is an abnormal heart rhythm related to an increased risk of heart failure, dementia, and stroke. The distinction between valvular and non-valvular AF remains a debate. In this study, proteomics and metabolomics were integrated to describe the dysregulated metabolites and proteins of AF patients relative to sinus rhythm (SR) patients. Totally 47 up-regulated and 41 down-regulated proteins in valvular AF, and 59 up-regulated and 149 down-regulated proteins in non-valvular AF were recognized in comparison to SR patients. Moreover, 58 up-regulated and 49 significantly down-regulated metabolites in valvular AF, and 47 up-regulated and 122 down-regulated metabolites in persistent non-valvular AF patients were identified in comparison to SR patients. Based on analysis of differential levels of metabolites and proteins, 15 up-regulated and 22 down-regulated proteins, and 13 up-regulated and 122 down-regulated metabolites in persistent non-valvular AF were identified relative to valvular AF. KEGG pathway enrichment analysis showed the altered proteins and metabolites were significantly related to multiple metabolic pathways, such as Glycolysis/Gluconeogenesis. Interestingly, the enrichment pathways related to non-valvular AF were obviously different from those in valvular AF. For example, valvular AF was significantly related to Glycolysis/Gluconeogenesis, but non-valvular AF was more related to Citrate cycle (TCA cycle). Correlation analysis between the differentially expressed proteins and metabolites was also performed. Several hub proteins with metabolites were identified in valvular AF and non-valvular AF. For example, Taurine, D-Threitol, L-Rhamnose, and DL-lactate played crucial roles in valvular AF, while Glycerol-3-phosphate dehydrogenase, Inorganic pyrophosphatase 2, Hydroxymethylglutaryl-CoAlyase, and Deoxyuridine 5-triphosphate nucleotidohydrolase were crucial in non-valvular AF. Then two hub networks were recognized as potential biomarkers, which can effectively distinguish valvular AF and non-valvular persistent AF from SR samples, with areas under curve of 0.75 and 0.707, respectively. Hence, these metabolites and proteins can be used as potential clinical molecular markers to discriminate two types of AF from SR samples. In summary, this study provides novel insights to understanding the mechanisms of AF progression and identifying novel biomarkers for prognosis of non-valvular AF and valvular AF by using metabolomics and proteomics analyses.
format article
author Bo Hu
Wen Ge
Yuliang Wang
Xiaobin Zhang
Tao Li
Hui Cui
Yongjun Qian
Yangyang Zhang
Zhi Li
author_facet Bo Hu
Wen Ge
Yuliang Wang
Xiaobin Zhang
Tao Li
Hui Cui
Yongjun Qian
Yangyang Zhang
Zhi Li
author_sort Bo Hu
title Metabolomic and Proteomic Analyses of Persistent Valvular Atrial Fibrillation and Non-Valvular Atrial Fibrillation
title_short Metabolomic and Proteomic Analyses of Persistent Valvular Atrial Fibrillation and Non-Valvular Atrial Fibrillation
title_full Metabolomic and Proteomic Analyses of Persistent Valvular Atrial Fibrillation and Non-Valvular Atrial Fibrillation
title_fullStr Metabolomic and Proteomic Analyses of Persistent Valvular Atrial Fibrillation and Non-Valvular Atrial Fibrillation
title_full_unstemmed Metabolomic and Proteomic Analyses of Persistent Valvular Atrial Fibrillation and Non-Valvular Atrial Fibrillation
title_sort metabolomic and proteomic analyses of persistent valvular atrial fibrillation and non-valvular atrial fibrillation
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/bcfeeb6b48d44ea3888898f22e277c49
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