Circular Network of Coregulated Sphingolipids Dictates Chronic Hypoxia Damage in Patients With Tetralogy of Fallot.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35097000", "kind": "science-record", "revision": 4, "content_hash": "sha256:764638f09a14bad49092ce113ff8b90340b91034c503be6b8657b11de84ce8ae", "created_at": "2026-11-01T17:36:49Z", "updated_at": "2026-11-01T21:27:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Circular Network of Coregulated Sphingolipids Dictates Chronic Hypoxia Damage in Patients With Tetralogy of Fallot.", "doi": "10.3389/fcvm.2021.780123", "pmid": "35097000", "authors": ["Na Zhou", "Libao Liu", "Rongjun Zou", "Minghui Zou", "Mingxia Zhang", "Fan Cao", "Wenhua Liu", "Huili Yuan", "Guodong Huang", "Li Ma", "Xinxin Chen"], "journal": "Frontiers in cardiovascular medicine", "year": 2021, "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.", "claims": [{"id": "claim-method", "statement": "The R package “clusterProfiler” was used to perform the GSEA of hub genes with RNA sequencing (RNA-seq) data (17).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35097000", "locator": "sections[5] \"Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA)\" paragraph 2", "quote": "The R package “clusterProfiler” was used to perform the GSEA of hub genes with RNA sequencing (RNA-seq) data (17)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO), https://www.ncbi.nlm.nih.gov/geo/, GSE132176 and GSE141955.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35097000", "locator": "sections[22] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO), https://www.ncbi.nlm.nih.gov/geo/, GSE132176 and GSE141955."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Sphingolipid metabolism was downregulated in TOF; however, the detailed mechanism needs further investigation.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35097000", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Sphingolipid metabolism was downregulated in TOF; however, the detailed mechanism needs further investigation."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Sphingolipid metabolism was downregulated in TOF; however, the detailed mechanism needs further investigation.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35097000"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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