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Войти в исследования BMC cardiovascular disorders · 2026
Multi-omics analysis of human right atrial tissue ıdentifies molecular signatures of remodeling in tricuspid regurgitation.
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Alma Melih, Aydın Ahmet, Sezer Aysima, Kablan Sevilay Erdoğan, Baysal İpek, Nemutlu Emirhan, Çiftçi Samiye Yabanoğlu, Yılmaz Mustafa
Аннотация
BACKGROUND: Tricuspid regurgitation (TR) is associated with adverse clinical outcomes, yet the underlying right atrial (RA) molecular remodeling remains poorly understood. We aimed to define TR-associated RA remodeling using metabolomic and lipidomic profiling of human RA tissue.
METHODS: RA appendage tissue was obtained intraoperatively from 24 adults undergoing cardiac surgery (11 with ≥severe TR; 13 controls). Gas chromatography mass spectrometry (GC-MS) was used for targeted small-molecule metabolomics, and liquid chromatography quadrupole time of flight mass spectrometry (LC-qTOF-MS) for untargeted lipidomics. Mann Whitney U testing, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and variable importance in projection (VIP) scoring were used to identify discriminatory multi-omics patterns between groups.
RESULTS: Patients with TR demonstrated a distinct metabolic phenotype characterized by reduced glycolysis-related intermediates (glucose-6-phosphate, β-alanine, α-glucosamine-1-phosphate; all p < 0.05) and metabolites consistent with oxidative stress and amino acid catabolism markers (6-hydroxycaproic acid, porphine, phosphoric acid; all p < 0.05). Lipidomic analysis revealed broad phospholipid remodeling and signals consistent with mitochondrial-associated alterations, including a decreased phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio and reductions in selected diacylglycerol and ceramide species. PCA and PLS-DA demonstrated clear group separation with consistent VIP signals, indicating consistent multi-omics discrimination.
CONCLUSIONS: TR is associated with coordinated metabolic and lipidomic reprogramming in the RA, a pattern compatible with, though not direct evidence of, mitochondrial stress, impaired bioenergetics, and membrane destabilization. These findings support a model in which RA remodeling is tightly linked to TR pathophysiology, highlighting candidate molecular features for future validation. Multi-omics biomarkers may enhance risk stratification, inform the timing of intervention, and guide the development of future point-of-care molecular diagnostics.
METHODS: RA appendage tissue was obtained intraoperatively from 24 adults undergoing cardiac surgery (11 with ≥severe TR; 13 controls). Gas chromatography mass spectrometry (GC-MS) was used for targeted small-molecule metabolomics, and liquid chromatography quadrupole time of flight mass spectrometry (LC-qTOF-MS) for untargeted lipidomics. Mann Whitney U testing, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and variable importance in projection (VIP) scoring were used to identify discriminatory multi-omics patterns between groups.
RESULTS: Patients with TR demonstrated a distinct metabolic phenotype characterized by reduced glycolysis-related intermediates (glucose-6-phosphate, β-alanine, α-glucosamine-1-phosphate; all p < 0.05) and metabolites consistent with oxidative stress and amino acid catabolism markers (6-hydroxycaproic acid, porphine, phosphoric acid; all p < 0.05). Lipidomic analysis revealed broad phospholipid remodeling and signals consistent with mitochondrial-associated alterations, including a decreased phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio and reductions in selected diacylglycerol and ceramide species. PCA and PLS-DA demonstrated clear group separation with consistent VIP signals, indicating consistent multi-omics discrimination.
CONCLUSIONS: TR is associated with coordinated metabolic and lipidomic reprogramming in the RA, a pattern compatible with, though not direct evidence of, mitochondrial stress, impaired bioenergetics, and membrane destabilization. These findings support a model in which RA remodeling is tightly linked to TR pathophysiology, highlighting candidate molecular features for future validation. Multi-omics biomarkers may enhance risk stratification, inform the timing of intervention, and guide the development of future point-of-care molecular diagnostics.