AUTHOR=Liu Libao , Huang Lei , Yao Lishuai , Zou Fan , He Jinyuan , Zhao Xiaodong , Mei Lugang , Huang Shuai 

TITLE=Energy metabolism disorder dictates chronic hypoxia damage in heart defect with tetralogy of fallot

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.1096664

DOI=10.3389/fcvm.2022.1096664

ISSN=2297-055X

ABSTRACT=Background: Tetralogy of Fallot (TOF) is the most common cyanotic heart damage. However, in the chronic myocardial hypoxia injury related to TOF, the potential molecular mechanism of cardiac energy metabolism is still unclear.
Methods: In this study, we used microarray transcriptome analysis and liquid chromatography tandem mass spectrometry (LC-MS/MS) metabonomics analysis methods to explore the energy metabolism pathway during chronic hypoxia injury. The gene expression synthesis (GEO) dataset GSE132176 was downloaded to analyze the metabolic pathways in TOF. Then, the clinical samples (right atrial tissues) of atrial septal defect (ASD) and TOF were analyzed by metabonomics. Next, we screened important pathways and important differential metabolites related to energy metabolism to explore the pathogenesis of TOF. 
Results: GSEA showed that the regulation of triglyceride metabolism, organic acid metabolism, lipid metabolism, retinol metabolism, retinoic acid metabolism, triglyceride metabolism and diterpene metabolism were significantly identified. GSVA results show that there is a significant difference between ASD group and TOF group in the positive regulation of terpene metabolism and triglyceride metabolism. pathways with significant enrichment (impact＞0.1) in TOF are caffeine metabolism(impact=0.69), tryptophan metabolism (impact=0.24), sphingolipid metabolism (impact=0.27).  Pathways with significant enrichment (impact＞0.1) in ASD are caffeine metabolism (impact=0.69), riboflavin metabolism (impact=0.5), D-Glutamine and D-glutamate metabolism (impact=0.5), alanine, aspartate and glutamate metabolism (impact=0.35), histidine metabolism (impact=0.34), cysteine and methionine metabolism (impact=0.33), tryptophan metabolism (impact=0.27), sphingolipid metabolism (impact=0.27), nicotinate and nicotinamide metabolism (impact=0.24), arginine biosynthesis (impact=0.23), glycerophospholipid metabolism (impact=0.16), amino sugar and nucleotide sugar metabolism (impact=0.12), arginine and proline metabolism (impact=0.11). 
Conclusion: Disturbed energy metabolism occurs in patients with TOF; further investigation was needed to further clarify mechanism.