Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan 18:9:1096664.
doi: 10.3389/fcvm.2022.1096664. eCollection 2022.

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

Libao Liu  1 , Lei Huang  2 , Lishuai Yao  1 , Fan Zou  1 , Jinyuan He  1 , Xiaodong Zhao  3   4 , Lugang Mei  5 , Shuai Huang  1
Affiliations

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

Libao Liu et al. Front Cardiovasc Med. .

Abstract

Background: Tetralogy of Fallot (TOF) belongs to cyanotic heart damage, which is the most common in clinic. In the chronic myocardial hypoxia injury related to TOF, the potential molecular mechanism of cardiac energy metabolism remains unclear.

Materials and methods: In our study, microarray transcriptome analysis and metabonomics methods were used to explore the energy metabolism pathway during chronic hypoxia injury. The gene expression omnibus (GEO) dataset GSE132176 was obtained for analyzing the metabolic pathways. 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: Gene set enrichment analysis (GSEA) indicated that fructose 6-phosphate metabolic process, triglyceride metabolic process, and et al. were significantly enriched. Gene set variation analysis (GSVA) results showed that significant difference of ASD group and TOF group existed in terpenoid metabolic process and positive regulation of triglyceride metabolic process. Pathways with significant enrichment (impact > 0.1) in TOF were caffeine metabolism (impact = 0.69), sphingolipid metabolism (impact = 0.46), glycerophospholipid metabolism (impact = 0.26), tryptophan metabolism (impact = 0.24), galactose metabolism (impact = 0.11). Pathways with significant enrichment (impact > 0.1) in ASD are caffeine metabolism (impact = 0.69), riboflavin metabolism (impact = 0.5), alanine, aspartate and glutamate metabolism (impact = 0.35), histidine metabolism (impact = 0.34) and et al.

Conclusion: Disturbed energy metabolism occurs in patients with TOF or ASD, and further investigation was needed to further clarify mechanism.

Keywords: congenital heart disease; energy metabolism; liquid chromatography tandem mass spectrometry; metabolomic analysis; tetralogy of fallot.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Differential expressed genes and gene ontology (GO) analysis in GSE132176 dataset. (A) Differentially expressed genes in tetralogy of fallot (TOF) vs. atrial septal defect (ASD). (B) GO analysis of down-regulated genes. (C) GO analysis of up-regulated genes.
FIGURE 2
FIGURE 2
Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA). (A) The energy metabolism-related pathways detected through GSEA analysis. (B) The heatmap of the GSVA score for the KEGG pathway. (C) The bar plot for patterns of the GSVA score of energy metabolism. (D) The energy metabolism- related pathways detected through GSEA analysis.
FIGURE 3
FIGURE 3
Pathway interaction analysis. (A) Pathway interworking network. (B) LogFC of genes in regulation of triglyceride metabolic process. (C) Protein-protein interactions network of genes in regulation of triglyceride metabolic process.
FIGURE 4
FIGURE 4
Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) of atrial septal defect (ASD) and tetralogy of fallot (TOF). (A) PCA for all samples. (B) Heatmap of sample distances. (C) OPLS-DA for ASD samples. (D) OPLS-DA for TOF samples. (E) Fitting analysis of ASD samples. (F) Fitting analysis of TOF samples. (G) S-plot analysis of metabolites in ASD samples. (H) S-plot analysis of metabolites in TOF samples.
FIGURE 5
FIGURE 5
Differential metabolite analysis. (A) Volcanogram of differential metabolites in atrial septal defect (ASD) samples. (B) Up- and down-regulated of the top 10 metabolites in ASD samples. (C) Top 20 differential metabolites by VIP value in ASD samples. (D) Volcanogram of differential metabolites in tetralogy of fallot (TOF) samples. (E) Up- and down-regulated of the top 10 metabolites in TOF samples. (F) Top 20 differential metabolites by VIP in TOF samples.
FIGURE 6
FIGURE 6
Differential metabolite enrichment analysis. (A) Heatmap of differential metabolites in atrial septal defect (ASD) samples. (B) Heatmap of differential metabolites in tetralogy of fallot (TOF) samples. (C) Heatmap of differential metabolite correlations in ASD samples. (D) Heatmap of differential metabolite correlations in TOF samples. (E) Metabolic pathways of ASD. (F) Metabolic pathways of TOF.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Sung JH, Sakamori R, Yamada R, Yoshioka T, Sakane S, Tahata Y, et al. Hepatocellular carcinoma in a patient with tetralogy of fallot: a case report and literature review. Internal Med. (2022) 61:1361–5. 10.2169/internalmedicine.7827-21 - DOI - PMC - PubMed
    1. Rahmath MRK, Boudjemline Y. Tetralogy of fallot will be treated interventionally within two decades. Pediatr Cardiol. (2020) 41:539–45. 10.1007/s00246-020-02297-z - DOI - PMC - PubMed
    1. Bedair R, Iriart X. EDUCATIONAL SERIES IN CONGENITAL HEART DISEASE: tetralogy of fallot: diagnosis to long-term follow-up. Echo Res Pract. (2019) 6:R9–23. 10.1530/ERP-18-0049 - DOI - PMC - PubMed
    1. Zhou N, Liu LB, Zou RJ, Zou MH, Zhang MX, Cao F, et al. Circular network of coregulated sphingolipids dictates chronic hypoxia damage in patients with tetralogy of fallot. Front Cardiovasc Med. (2022) 8:780123. 10.3389/fcvm.2021.780123 - DOI - PMC - PubMed
    1. Apostolopoulou SC, Manginas A, Kelekis NL, Noutsias M. Cardiovascular imaging approach in pre and postoperative tetralogy of fallot. BMC Cardiovasc Disord. (2019) 19:7. 10.1186/s12872-018-0996-9 - DOI - PMC - PubMed

LinkOut - more resources