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Biomarkers and key pathways in atrial fibrillation associated with mitral valve disease identified by multi-omics study

BACKGROUND: Mitral valve disease (MVD)-associated atrial fibrillation (AF) is one of the most common arrhythmias with an increased risk of thromboembolic events. This study aimed to identify the molecular mechanisms and possible biomarkers for chronic AF in MVD by using multi-omics methods. METHODS:...

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Autores principales: Li, Ming-Yang, Chen, Huan-Xin, Hou, Hai-Tao, Wang, Jun, Liu, Xiao-Cheng, Yang, Qin, He, Guo-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033373/
https://www.ncbi.nlm.nih.gov/pubmed/33842614
http://dx.doi.org/10.21037/atm-20-3767
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author Li, Ming-Yang
Chen, Huan-Xin
Hou, Hai-Tao
Wang, Jun
Liu, Xiao-Cheng
Yang, Qin
He, Guo-Wei
author_facet Li, Ming-Yang
Chen, Huan-Xin
Hou, Hai-Tao
Wang, Jun
Liu, Xiao-Cheng
Yang, Qin
He, Guo-Wei
author_sort Li, Ming-Yang
collection PubMed
description BACKGROUND: Mitral valve disease (MVD)-associated atrial fibrillation (AF) is one of the most common arrhythmias with an increased risk of thromboembolic events. This study aimed to identify the molecular mechanisms and possible biomarkers for chronic AF in MVD by using multi-omics methods. METHODS: This prospective study enrolled patients with MVD (n=100) undergoing mitral valve replacement surgery. The patients were allocated into chronic AF and sinus rhythm (SR) groups. Plasma samples were collected preoperatively. Proteomics was performed with isobaric tags for relative and absolute quantitation (iTRAQ) to identify differential proteins (DPs) between the two groups. The selected DPs were then validated in a new cohort of patients by enzyme-linked immunosorbent assay (ELISA). A gas chromatography-mass spectrometer was used in the metabolomics study to identify differential metabolites (DMs). Bioinformatics analyses were performed to analyze the results. RESULTS: Among the 447 plasma proteins and 322 metabolites detected, 57 proteins and 55 metabolites, including apolipoprotein A-I (ApoA-I), apolipoprotein A-II (ApoA-II), LIM domain only protein 7 (LMO7), and vitronectin (VN) were differentially expressed between AF and SR patients. Bioinformatics analyses identified enriched pathways related to AF, including peroxisome proliferator-activated receptor alpha (PPARα), the renin angiotensin aldosterone system (RAAS), galactose, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism. CONCLUSIONS: Using integrated multi-omics technologies in MVD-associated AF patients, the present study, for the first time, revealed important signaling pathways, such as PPARα, as well as possible roles of other signaling pathways, including the RAAS and galactose metabolism to understand the molecular mechanism of MVD-associated AF. It also identified a large number of DPs and DMs. Some identified proteins and metabolites, such as ApoA-I, ApoA-II, LMO7, and VN, may be further developed as biomarkers for MVD-associated AF.
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spelling pubmed-80333732021-04-09 Biomarkers and key pathways in atrial fibrillation associated with mitral valve disease identified by multi-omics study Li, Ming-Yang Chen, Huan-Xin Hou, Hai-Tao Wang, Jun Liu, Xiao-Cheng Yang, Qin He, Guo-Wei Ann Transl Med Original Article BACKGROUND: Mitral valve disease (MVD)-associated atrial fibrillation (AF) is one of the most common arrhythmias with an increased risk of thromboembolic events. This study aimed to identify the molecular mechanisms and possible biomarkers for chronic AF in MVD by using multi-omics methods. METHODS: This prospective study enrolled patients with MVD (n=100) undergoing mitral valve replacement surgery. The patients were allocated into chronic AF and sinus rhythm (SR) groups. Plasma samples were collected preoperatively. Proteomics was performed with isobaric tags for relative and absolute quantitation (iTRAQ) to identify differential proteins (DPs) between the two groups. The selected DPs were then validated in a new cohort of patients by enzyme-linked immunosorbent assay (ELISA). A gas chromatography-mass spectrometer was used in the metabolomics study to identify differential metabolites (DMs). Bioinformatics analyses were performed to analyze the results. RESULTS: Among the 447 plasma proteins and 322 metabolites detected, 57 proteins and 55 metabolites, including apolipoprotein A-I (ApoA-I), apolipoprotein A-II (ApoA-II), LIM domain only protein 7 (LMO7), and vitronectin (VN) were differentially expressed between AF and SR patients. Bioinformatics analyses identified enriched pathways related to AF, including peroxisome proliferator-activated receptor alpha (PPARα), the renin angiotensin aldosterone system (RAAS), galactose, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism. CONCLUSIONS: Using integrated multi-omics technologies in MVD-associated AF patients, the present study, for the first time, revealed important signaling pathways, such as PPARα, as well as possible roles of other signaling pathways, including the RAAS and galactose metabolism to understand the molecular mechanism of MVD-associated AF. It also identified a large number of DPs and DMs. Some identified proteins and metabolites, such as ApoA-I, ApoA-II, LMO7, and VN, may be further developed as biomarkers for MVD-associated AF. AME Publishing Company 2021-03 /pmc/articles/PMC8033373/ /pubmed/33842614 http://dx.doi.org/10.21037/atm-20-3767 Text en 2021 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Li, Ming-Yang
Chen, Huan-Xin
Hou, Hai-Tao
Wang, Jun
Liu, Xiao-Cheng
Yang, Qin
He, Guo-Wei
Biomarkers and key pathways in atrial fibrillation associated with mitral valve disease identified by multi-omics study
title Biomarkers and key pathways in atrial fibrillation associated with mitral valve disease identified by multi-omics study
title_full Biomarkers and key pathways in atrial fibrillation associated with mitral valve disease identified by multi-omics study
title_fullStr Biomarkers and key pathways in atrial fibrillation associated with mitral valve disease identified by multi-omics study
title_full_unstemmed Biomarkers and key pathways in atrial fibrillation associated with mitral valve disease identified by multi-omics study
title_short Biomarkers and key pathways in atrial fibrillation associated with mitral valve disease identified by multi-omics study
title_sort biomarkers and key pathways in atrial fibrillation associated with mitral valve disease identified by multi-omics study
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033373/
https://www.ncbi.nlm.nih.gov/pubmed/33842614
http://dx.doi.org/10.21037/atm-20-3767
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