Identification of Ferroptosis-Related Genes in Heart Failure Induced by Transverse Aortic Constriction.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37927963", "kind": "science-record", "revision": 4, "content_hash": "sha256:85adbbbd2915447d759bc171922f62f5d39bbf36fc93b283d0071e81bb387ace", "created_at": "2026-11-01T19:02:49Z", "updated_at": "2026-11-01T22:10:35Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Ferroptosis-Related Genes in Heart Failure Induced by Transverse Aortic Constriction.", "doi": "10.2147/JIR.S433387", "pmid": "37927963", "authors": ["Jian Jun Gu", "Tian Jian Du", "Li Na Zhang", "Jing Zhou", "Xiang Gu", "Ye Zhu"], "journal": "Journal of inflammation research", "year": 2023, "abstract": "Background: Heart failure (HF) is a common clinical syndrome due to ventricular dysfunction and is a major cause of mortality worldwide. Ferroptosis, marked by excessive iron-dependent lipid peroxidation, is closely related to HF. Therefore, the purpose of this study is to explore and validate ferroptosis-related markers in HF by bioinformatics analysis and animal experiments validation.\nMaterials and Methods: The gene expression profiles (GSE36074) of murine transverse aortic constriction (TAC) were obtained from the Gene Expression Omnibus (GEO); From the FerrDb database, ferroptosis-related genes (FRGs) were identified. Using GEO2R, differential expressed genes (DEGs) were screened. An overlapping analysis was conducted among DEGs and FRGs to identify ferroptosis-related DEGs (FRDEGs). We then performed clustering, functional enrichment analysis, and protein-protein interaction (PPI) analyses. In addition, the key FRDEGs were extracted by cytoHubba plugin and the networks of transcription factors (TFs)-key FRDEGs and microRNA-key FRDEGs were constructed. Lastly, the key FRDEGs were carried by quantitative reverse transcription PCR (RT-qPCR) and immunohistochemistry (IHC).\nResults: Fifty-nine FRGs showing significantly different expression were identified from a total of 1918 DEGs in mice heart by transverse aortic constriction. GO and KEGG functional enrichment analysis revealed that these 59 ferroptosis-related DEGs mostly associated with positive regulation of apoptotic process, FoxO signaling pathway, VEGF signaling pathway, Apoptosis, Ferroptosis. Five key FRDEGs (Mapk14, Hif1a, Ddit3, Tlr4 and Ptgs2) were identified using PPI networks; Based on TFs-key FRDEGs networks, we found that Mapk14, Hif1a, Tlr4 and Ptgs2 were regulated by 3, 4, 5, and 29 TFs, respectively; however, Ddit3 was not regulated by any TF; By analyzing the miRNA-key FRDEGs networks, we found that 39, 74, 11, 28, and 18 miRNAs targets regulate the expression of Mapk14, Hif1a, Ddit3, Tlr4 and Ptgs2, respectively. Lastly, five key FRDEGs were validated at the mRNA and protein levels by RT-qPCR and IHC, which were in line with our bioinformatics analysis.\nConclusion: Our findings reveal that Mapk14, Hif1a, Ddit3, Tlr4 and Ptgs2 may be involved in the development of HF through regulating ferroptosis and as potential targets for HF.", "claims": [{"id": "claim-method", "statement": "A two-sample unpaired Student’s t-test was used for two-group comparisons.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37927963", "locator": "sections[13] \"Statistical Analysis\" paragraph 2", "quote": "A two-sample unpaired Student’s t-test was used for two-group comparisons."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data is available in NCBI GEO, accession number: GSE36074 and ementary material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37927963", "locator": "sections[25] \"Data Sharing Statement\" paragraph 2", "quote": "The data is available in NCBI GEO, accession number: GSE36074 and ementary material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our findings reveal that Mapk14, Hif1a, Ddit3, Tlr4 and Ptgs2 may be involved in the development of HF through regulating ferroptosis and as potential targets for HF.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37927963", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Our findings reveal that Mapk14, Hif1a, Ddit3, Tlr4 and Ptgs2 may be involved in the development of HF through regulating ferroptosis and as potential targets for HF."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Our findings reveal that Mapk14, Hif1a, Ddit3, Tlr4 and Ptgs2 may be involved in the development of HF through regulating ferroptosis and as potential targets for HF.", "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:37927963"], "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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GO", ", humidity of 55% and 12 h light/dark cycle. Mice were fed a standard pellet diet and water ad libi", "was cleaned regularly by professionals. All mice were anesthetized with ketamine (80 mg/kg) and xy"], "order_basis": "paper_text_order:516", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["d by quantitative reverse transcription PCR (RT-qPCR) and immunohistochemistry (IHC). Results: Fi", "validated at the mRNA and protein levels by RT-qPCR and IHC, which were in line with our bioinfo", "y quantitative reverse transcription PCR (RT-qPCR) and immunohistochemistry (IHC). 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