Abstract
Introduction: Right and left atria have different susceptibilities toward developing atrial fibrillation (AF). The molecular bases of these differences are not well characterized. Given the complexity of AF development and progression, understanding AF-associated changes in myocardial energetics between the atria will help improve mechanistic insights and therapeutics for better clinical management of AF. The aim was to compare changes in mitochondrial oxidative phosphorylation system (OXPHOS), glycolysis and Krebs cycle metabolites in right atrial (RAA) and left atrial (LAA) appendage tissue from patients with (AF) and without (non-AF) AF. Methods: RAA and LAA from well-matched AF (n=54) and non-AF (n=58) patients undergoing elective open heart surgery was collected. Functional activity of OXPHOS complexes I-V was measured spectrophotometrically. Protein expression level of OXPHOS complexes was determined by Western blot. OXPHOS gene expression level was performed using RT-PCR. Metabolites were profiled using high performance liquid chromatography coupled to tandem mass spectrometry. Comparison between groups was done applying the 2 sample t - and Wilcoxon rank sum tests with 5% level of significance. Results: The most significant AF-associated alterations in myocardial energetics were observed in RAA. In AF patients, out of 84 OXPHOS genes, expression of 14 genes was significantly reduced in RAA (p<0.05) and 2 genes was reduced in LAA (p<0.05). There was AF-associated reduction in complex I (p=0.01) and IV (p=0.04) protein expression in RAA without changes in LAA. Unlike LAA, mitochondria from RAA revealed decline in complex I (p=0.01) and II (p=0.03) activity in AF compared to non-AF patients. In AF patients, glycolysis metabolites level of glucose-6-phosphate and phosphoenolpyruvate was reduced in RAA (p=0.03), whereas 2-phosphoglycerate was reduced in LAA (p=0.02). AF was related with decrease in NAD + (p=0.03), GDP (p=0.05), citrate (p=0.03), total pool of adenine nucleotides (p=0.02) and glutathione (p=0.03) level in RAA without changes in LAA. Conclusion: AF is associated with different energetic remodeling in right and left atria, suggesting that dissimilar mechanisms may contribute to development and progression of AF.
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