In:
Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 8 ( 2022-1-13)
Abstract:
Background: Tetralogy of Fallot (TOF) is the most common cyanotic heart disease. However, the association of cardiac metabolic reprogramming changes and underlying molecular mechanisms in TOF-related chronic myocardial hypoxia damage are still unclear. Methods: In this study, we combined microarray transcriptomics analysis with liquid chromatography tandem-mass spectrometry (LC–MS/MS) spectrum metabolomics analysis to establish the metabolic reprogramming that occurs in response to chronic hypoxia damage. Two Gene Expression Omnibus (GEO) datasets, GSE132176 and GSE141955, were downloaded to analyze the metabolic pathway in TOF. Then, a metabolomics analysis of the clinical samples (right atrial tissue and plasma) was performed. Additionally, an association analysis between differential metabolites and clinical phenotypes was performed. Next, four key genes related to sphingomyelin metabolism were screened and their expression was validated by real-time quantitative PCR (QT-PCR). Results: The gene set enrichment analysis (GSEA) showed that sphingolipid metabolism was downregulated in TOF and the metabolomics analysis showed that multiple sphingolipids were dysregulated. Additionally, genes related to sphingomyelin metabolism were identified. We found that four core genes, UDP-Glucose Ceramide Glucosyltransferase ( UGCG ), Sphingosine-1-Phosphate Phosphatase 2 ( SGPP2 ), Fatty Acid 2-Hydroxylase ( FA2H ), and Sphingosine-1-Phosphate Phosphatase 1 ( SGPP1 ), were downregulated in TOF. Conclusion: Sphingolipid metabolism was downregulated in TOF; however, the detailed mechanism needs further investigation.
Type of Medium:
Online Resource
ISSN:
2297-055X
DOI:
10.3389/fcvm.2021.780123
DOI:
10.3389/fcvm.2021.780123.s001
DOI:
10.3389/fcvm.2021.780123.s002
DOI:
10.3389/fcvm.2021.780123.s003
DOI:
10.3389/fcvm.2021.780123.s004
DOI:
10.3389/fcvm.2021.780123.s005
DOI:
10.3389/fcvm.2021.780123.s006
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2781496-8
