Background: Cyanotic congenital heart disease (CCHD) is one of the most common birth anomalies, in which chronic hypoxia is the basic pathophysiological process.
Methods: To investigate the heart's metabolic remodeling to hypoxia, we performed an untargeted metabolomic analysis of cardiac tissue from 20 CCHD patients and 15 patients with acyanotic congenital heart disease (ACHD).
Results: A total of 71 (63%) metabolites from 113 detected substances in cardiac tissue differed between the CCHD and ACHD groups. A partial least squares discriminant analysis showed separation between the CCHD and ACHD groups. A pathway enrichment analysis revealed that the most enriched metabolic pathways were amino acid metabolism and energy metabolism. Eleven amino acids were increased in CCHD patients, indicating that protein synthesis was down-regulated. Most of the metabolites in Krebs circle were increased in CCHD patients, suggesting down regulation of aerobic energy metabolism. Hierarchical cluster analysis showed that nicotinamide adenine dinucleotide (NAD) was clustered with Krebs cycle related substrates and its level was significantly higher in CCHD than that in ACHD patients. These analyses suggest that NAD might play an important role in response to hypoxia in CCHD patients.
Conclusion: Our data showed a significantly different metabolic profile in CCHD patients compared to ACHD patients, including reduced protein synthesis and aerobic energy production, and the increased level of NAD in the myocardium may be a response mechanism to hypoxia.
Keywords: Congenital heart disease; Krebs cycle; chronic hypoxia; metabolomics; nicotinamide adenine dinucleotide.
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