Biomedicines · 2024
Specific Multiomic Profiling in Aortic Stenosis in Bicuspid Aortic Valve Disease.
СтатьяНазвание и аннотация: Перевод в очереди
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Antequera-González Borja, Martínez-Micaelo Neus, Sureda-Barbosa Carlos, Galian-Gay Laura, Siliato-Robles M Sol, Ligero Carmen, Evangelista Artur, Alegret Josep M
Аннотация
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.
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.