Key result
Bicuspid aortic valves with severe aortic stenosis exhibited a distinct RNA and metabolic profile linked to mitochondrial dysfunction and oxidative stress compared to tricuspid aortic valves.
Why the study?
BAV disease is linked to faster valve degeneration and high AS incidence, but differences in AS pathophysiology between BAV and TAV patients remain unclear.
Does the multiomic profile of severe aortic stenosis differ between patients with bicuspid versus tricuspid aortic valves?
Observational (n=18)
Does the multiomic profile of severe aortic stenosis differ between patients with bicuspid versus tricuspid aortic valves?
This study identifies specific multiomic differences in the pathophysiology of severe aortic stenosis between bicuspid and tricuspid aortic valves, highlighting mitochondrial dysfunction and oxidative stress in BAV.
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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Antequera-González et al. (2024) conducted an observational in Severe aortic stenosis (n=18). Bicuspid aortic valve (BAV) vs. Tricuspid aortic valve (TAV) was evaluated on Multiomic profile (RNA expression and metabolic profile). Bicuspid aortic valves with severe aortic stenosis exhibited a distinct RNA and metabolic profile linked to mitochondrial dysfunction and oxidative stress compared to tricuspid aortic valves.
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