Specific Multiomic Profiling in Aortic Stenosis in Bicuspid Aortic Valve Disease

Area of Science:

• Cardiovascular Research
• Genomics and Metabolomics
• Pathophysiology

Background:

• Bicuspid aortic valve (BAV) disease is linked to accelerated aortic valve degeneration and a high incidence of aortic stenosis (AS).
• Understanding the specific pathophysiology of AS in BAV patients compared to tricuspid aortic valve (TAV) patients is crucial for targeted therapies.

Purpose of the Study:

• To identify distinct pathophysiological differences in AS between BAV and TAV patients.
• To integrate multiomics data (metabolomics, transcriptomics) with clinical data for a comprehensive profile of AS in BAV disease.

Main Methods:

• A multiomics approach was used, including RNA sequencing (RNA-seq) and proton nuclear magnetic resonance spectroscopy (1H-NMR) on aortic valve tissue from 18 patients (10 BAV, 8 TAV) with severe AS.
• Clinical data was integrated with transcriptomic and metabolomic profiles.
• Differential expression analysis and functional enrichment were performed.

Main Results:

• Metabolomic analysis revealed distinct metabolic profiles in BAV patients with AS compared to TAV patients.
• Transcriptomic analysis showed differential RNA expression between the groups, linked to mitochondrial dysfunction.
• Integrated multiomics data suggested mitochondrial dysfunction and oxidative stress as central to AS pathophysiology in BAV disease.

Conclusions:

• The pathophysiology of AS in BAV disease is distinct from TAV-associated AS, characterized by a specific RNA and metabolic signature.
• Mitochondrial dysfunction and increased oxidative stress are identified as key contributors to AS in BAV patients.