Specific Multiomic Profiling in Aortic Stenosis in Bicuspid Aortic Valve Disease

Introduction and purpose: Bicuspid aortic valve (BAV) disease is associated with faster aortic valve degeneration and a high incidence of aortic stenosis (AS). In this study, we aimed to identify differences in the pathophysiology of AS between BAV and tricuspid aortic valve (TAV) patients in a mult...

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Main Authors: Borja Antequera-González, Neus Martínez-Micaelo, Carlos Sureda-Barbosa, Laura Galian-Gay, M. Sol Siliato-Robles, Carmen Ligero, Artur Evangelista, Josep M. Alegret
Format: Article
Language:English
Published: MDPI AG 2024-02-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/12/2/380
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author Borja Antequera-González
Neus Martínez-Micaelo
Carlos Sureda-Barbosa
Laura Galian-Gay
M. Sol Siliato-Robles
Carmen Ligero
Artur Evangelista
Josep M. Alegret
author_facet Borja Antequera-González
Neus Martínez-Micaelo
Carlos Sureda-Barbosa
Laura Galian-Gay
M. Sol Siliato-Robles
Carmen Ligero
Artur Evangelista
Josep M. Alegret
author_sort Borja Antequera-González
collection DOAJ
description Introduction and purpose: Bicuspid aortic valve (BAV) disease is associated with faster aortic valve degeneration and a high incidence of aortic stenosis (AS). In this study, we aimed to identify differences in the pathophysiology of AS between BAV and tricuspid aortic valve (TAV) patients in a multiomics study integrating metabolomics and transcriptomics as well as clinical data. Methods: Eighteen patients underwent aortic valve replacement due to severe aortic stenosis: 8 of them had a TAV, while 10 of them had a BAV. RNA sequencing (RNA-seq) and proton nuclear magnetic resonance spectroscopy (1H-NMR) were performed on these tissue samples to obtain the RNA profile and lipid and low-molecular-weight metabolites. These results combined with clinical data were posteriorly compared, and a multiomic profile specific to AS in BAV disease was obtained. Results: H-NMR results showed that BAV patients with AS had different metabolic profiles than TAV patients. RNA-seq also showed differential RNA expression between the groups. Functional analysis helped connect this RNA pattern to mitochondrial dysfunction. Integration of RNA-seq, 1H-NMR and clinical data helped create a multiomic profile that suggested that mitochondrial dysfunction and oxidative stress are key players in the pathophysiology of AS in BAV disease. Conclusions: The pathophysiology of AS in BAV disease differs from patients with a TAV and has a specific RNA and metabolic profile. This profile was associated with mitochondrial dysfunction and increased oxidative stress.
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spelling doaj.art-48c2c43ff3d045e480bdb9589b52f4f42024-02-23T15:08:40ZengMDPI AGBiomedicines2227-90592024-02-0112238010.3390/biomedicines12020380Specific Multiomic Profiling in Aortic Stenosis in Bicuspid Aortic Valve DiseaseBorja Antequera-González0Neus Martínez-Micaelo1Carlos Sureda-Barbosa2Laura Galian-Gay3M. Sol Siliato-Robles4Carmen Ligero5Artur Evangelista6Josep M. Alegret7Group of Cardiovascular Research, Pere Virgili Health Research Institute (IISPV), Universitat Rovira i Virgili, 43204 Reus, SpainGroup of Cardiovascular Research, Pere Virgili Health Research Institute (IISPV), Universitat Rovira i Virgili, 43204 Reus, SpainCardiac Surgery Department, Hospital Vall d’Hebron (CIBERCV), Universitat Autonoma de Barcelona, 08035 Barcelona, SpainCardiology Department, Hospital Vall d’Hebron (CIBERCV), Universitat Autonoma de Barcelona, 08035 Barcelona, SpainCardiac Surgery Department, Hospital Vall d’Hebron (CIBERCV), Universitat Autonoma de Barcelona, 08035 Barcelona, SpainGroup of Cardiovascular Research, Pere Virgili Health Research Institute (IISPV), Universitat Rovira i Virgili, 43204 Reus, SpainCardiology Department, Hospital Vall d’Hebron (CIBERCV), Universitat Autonoma de Barcelona, 08035 Barcelona, SpainGroup of Cardiovascular Research, Pere Virgili Health Research Institute (IISPV), Universitat Rovira i Virgili, 43204 Reus, SpainIntroduction and purpose: Bicuspid aortic valve (BAV) disease is associated with faster aortic valve degeneration and a high incidence of aortic stenosis (AS). In this study, we aimed to identify differences in the pathophysiology of AS between BAV and tricuspid aortic valve (TAV) patients in a multiomics study integrating metabolomics and transcriptomics as well as clinical data. Methods: Eighteen patients underwent aortic valve replacement due to severe aortic stenosis: 8 of them had a TAV, while 10 of them had a BAV. RNA sequencing (RNA-seq) and proton nuclear magnetic resonance spectroscopy (1H-NMR) were performed on these tissue samples to obtain the RNA profile and lipid and low-molecular-weight metabolites. These results combined with clinical data were posteriorly compared, and a multiomic profile specific to AS in BAV disease was obtained. Results: H-NMR results showed that BAV patients with AS had different metabolic profiles than TAV patients. RNA-seq also showed differential RNA expression between the groups. Functional analysis helped connect this RNA pattern to mitochondrial dysfunction. Integration of RNA-seq, 1H-NMR and clinical data helped create a multiomic profile that suggested that mitochondrial dysfunction and oxidative stress are key players in the pathophysiology of AS in BAV disease. Conclusions: The pathophysiology of AS in BAV disease differs from patients with a TAV and has a specific RNA and metabolic profile. This profile was associated with mitochondrial dysfunction and increased oxidative stress.https://www.mdpi.com/2227-9059/12/2/380aortic valveaortic stenosismitochondrial dysfunctionoxidative stressendothelial damagemetabolomics
spellingShingle Borja Antequera-González
Neus Martínez-Micaelo
Carlos Sureda-Barbosa
Laura Galian-Gay
M. Sol Siliato-Robles
Carmen Ligero
Artur Evangelista
Josep M. Alegret
Specific Multiomic Profiling in Aortic Stenosis in Bicuspid Aortic Valve Disease
Biomedicines
aortic valve
aortic stenosis
mitochondrial dysfunction
oxidative stress
endothelial damage
metabolomics
title Specific Multiomic Profiling in Aortic Stenosis in Bicuspid Aortic Valve Disease
title_full Specific Multiomic Profiling in Aortic Stenosis in Bicuspid Aortic Valve Disease
title_fullStr Specific Multiomic Profiling in Aortic Stenosis in Bicuspid Aortic Valve Disease
title_full_unstemmed Specific Multiomic Profiling in Aortic Stenosis in Bicuspid Aortic Valve Disease
title_short Specific Multiomic Profiling in Aortic Stenosis in Bicuspid Aortic Valve Disease
title_sort specific multiomic profiling in aortic stenosis in bicuspid aortic valve disease
topic aortic valve
aortic stenosis
mitochondrial dysfunction
oxidative stress
endothelial damage
metabolomics
url https://www.mdpi.com/2227-9059/12/2/380
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