5fd59021980a8d5604ec1f4b58286162 pmc_10887224.pdf 076881ac98d3fbc4236b8bbb6a3e7bbf41654610 pmc_10887224.pdf ca9adef3b7a05b073d0b25bb7e818c2b5a1f1c1f6f1b06db769dd8bfd6a63826 pmc_10887224.pdf Title: Specific Multiomic Profiling in Aortic Stenosis in Bicuspid Aortic Valve Disease Subject: 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. Keywords: aortic valve; aortic stenosis; mitochondrial dysfunction; oxidative stress; endothelial damage; metabolomics; transcriptome Author: Borja Antequera-González, Neus Martínez-Micaelo, Carlos Sureda-Barbosa, Laura Galian-Gay, M. Sol Siliato-Robles, Carmen Ligero, Artur Evangelista and Josep M. 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SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 519 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Methods Destination: section.2 Children: Item: Title: Patients Destination: subsection.2.1 Item: Title: Aortic Tissue Extraction Destination: subsection.2.2 Item: Title: Tissue Homogenization Destination: subsection.2.3 Item: Title: RNA-Seq Destination: subsection.2.4 Item: Title: Gene Enrichment Analysis Destination: subsection.2.5 Item: Title: Lipid Profile and Low-Molecular-Weight Metabolite Quantification by 1H-NMR Destination: subsection.2.6 Item: Title: Statistical Analysis and Multiomics Integrative Analysis Destination: subsection.2.7 Item: Title: Ethics Destination: subsection.2.8 Item: Title: Results Destination: section.3 Children: Item: Title: Clinical Characteristics of the Cohort Destination: subsection.3.1 Item: Title: RNA Pattern Depends on Aortic Valve Morphology in AS Destination: subsection.3.2 Item: Title: The Metabolic Profile Seems to Be Specified by the Aortic Valve Morphology Destination: subsection.3.3 Item: Title: Integrative Analysis of Clinical, 1H-NMR and RNA-Seq Data Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Specific Multiomic Profiling in Aortic Stenosis in Bicuspid Aortic Valve Disease Author: Borja Antequera-González, Neus Martínez-Micaelo, Carlos Sureda-Barbosa, Laura Galian-Gay, M. Sol Siliato-Robles, Carmen Ligero, Artur Evangelista and Josep M. Alegret Subject: 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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