Specific Multiomic Profiling in Aortic Stenosis in Bicuspid Aortic Valve Disease
Antequera-González, Borja (Universitat Rovira i Virgili)
Martínez-Micaelo, Neus (Universitat Rovira i Virgili)
Sureda-Barbosa, Carlos (Hospital Universitari Vall d'Hebron)
Galian-Gay, Laura (Hospital Universitari Vall d'Hebron)
Siliato-Robles, M. Sol (Hospital Universitari Vall d'Hebron)
Ligero, Carmen (Universitat Rovira i Virgili)
Evangelista Masip, Arturo (Hospital Universitari Vall d'Hebron)
Alegret i Colomé, Josep Maria (Universitat Rovira i Virgili)
Universitat Autònoma de Barcelona

Date:	2024
Abstract:	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.
Grants:	Instituto de Salud Carlos III FISPI18/00517
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Aortic valve ; Aortic stenosis ; Mitochondrial dysfunction ; Oxidative stress ; Endothelial damage ; Metabolomics ; Transcriptome
Published in:	Biomedicines, Vol. 12 (february 2024) , ISSN 2227-9059

DOI: 10.3390/biomedicines12020380
PMID: 38397982

14 p, 1.8 MB

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