Comprehensive analysis of aging-related genes and immune infiltration landscape in ischemic cardiomyopathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41019433", "kind": "science-record", "revision": 3, "content_hash": "sha256:ce0daeae8710dd2d6c1677f9567257cf9109109b8a1b76aa84e6e7cc7d1f63cb", "created_at": "2026-11-01T20:31:05Z", "updated_at": "2026-11-01T22:14:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive analysis of aging-related genes and immune infiltration landscape in ischemic cardiomyopathy.", "doi": "10.3389/fcvm.2025.1653314", "pmid": "41019433", "authors": ["Zhichao Wu", "Liang Du", "Xunfu Zhang", "Chengyu Jin", "Jinshan Ma"], "journal": "Frontiers in cardiovascular medicine", "year": 2025, "abstract": "Background: Ischemic cardiomyopathy (ICM), which arises from obstructive coronary artery diseases, is a leading cause of heart failure. Aging is a major risk factor for cardiovascular diseases, yet its connection to ICM remains unclear. This study aimed to investigate the role of aging-related gene expression in the context of ICM.\nMethods: Human microarray data (GSE116250) were retrieved from the GEO database and aging-related differentially expressed genes (ARDEGs) were identified using the Aging Atlas database. Functional enrichment and protein-protein interaction (PPI) network analyses were performed to elucidate the functions and interactions of these ARDEGs, leading to the identification of hub genes. The immune infiltration landscape in ICM was further characterized. Subsequently, integrated regulatory networks involving the hub genes were constructed through microRNA-mRNA-transcription factor interaction and GeneMANIA analyses, while their biological functions were inferred via gene set enrichment analysis (GSEA). The predictive value of the hub genes was validated using receiver operating characteristic (ROC) analysis based on both the identification dataset (GSE116250) and an independent validation cohort (GSE1145) Finally,the expression patterns of these genes were verified by RT-qPCR on mouse disease model.\nResults: A total of 50 ARDEGs (42 upregulated and 8 downregulated) were identified,which are primarily involved in the response to inflammation. Ten types of immune cells showed significant alterations in the ICM heart tissues. Among these cells, CD56dim NK cells exhibited extensive and significant correlations with other immune cells. JUN was identified as a key transcription factor regulating the top five hub ARDEGs: TNF, PTGS2, IL6, IL1B, and CXCL8. ROC analysis demonstrated that TNF, CXCL8, and IL6 serve as potential biomarkers for ICM, and the combination of the three markers further improved the predictive value. RT-qPCR analysis subsequently confirmed the upregulation of these hub inflammatory ARDEGs in mouse heart tissues.\nConclusion: Aging-related genes play a significant role in ICM and targeting these genes may pave the way for ICM diagnostic and therapeutic strategies.", "claims": [{"id": "claim-method", "statement": "Comparisons between the two groups were performed by using T-test analysis in GraphPad Prism (9.5.0).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41019433", "locator": "sections[16] \"Statistical analysis\" paragraph 2", "quote": "Comparisons between the two groups were performed by using T-test analysis in GraphPad Prism (9.5.0)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/geo/), accession numbers: GSE116250 and GSE1145.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41019433", "locator": "sections[30] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/geo/), accession numbers: GSE116250 and GSE1145."}], "state": "complete"}, {"id": "claim-target-result", "statement": "As expected, compared to the control group, the expression levels of Il6, Tnf, and IL1b were significantly upregulated in the MI group (P < 0.05, Figures 8D–F).", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "As expected, compared to the control group, the expression levels of Il6, Tnf, and IL1b were significantly upregulated in the MI group (P < 0.05, Figures 8D–F)."}, "evidence": [{"asset": "source:pmid:41019433", "locator": "sections[25] \"Expression validation of hub ARDEGs in mouse MI model\" paragraph 2", "quote": "As expected, compared to the control group, the expression levels of Il6, Tnf, and IL1b were significantly upregulated in the MI group (P < 0.05, Figures 8D–F)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "As expected, compared to the control group, the expression levels of Il6, Tnf, and IL1b were significantly upregulated in the MI group (P < 0.05, Figures 8D–F).", "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:41019433"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE1145"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE1145"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41019433", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcvm.2025.1653314", "sha256": "sha256:89c9359f7b3f72e569714cd138ab443bfeb8b62d4fbb878df78e4127febf432c", "bytes": 60972, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcvm.2025.1653314", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12461871", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE1145", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE1145", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE1145", "version": null, "note": "Publicly available datasets were analyzed in this study. 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Methods: Human microarray data (GSE116250) were retrieved from the GEO"], "order_basis": "paper_text_order:412", "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": ["ion patterns of these genes were verified by RT-qPCR on mouse disease model. Results: A total of", "rkers further improved the predictive value. RT-qPCR analysis subsequently confirmed the upregula", "patterns of these genes were verified by RT-qPCR on mouse disease model. Results: A total of", "rs further improved the predictive value. RT-qPCR analysis subsequently confirmed the upregula"], "order_basis": "paper_text_order:1372", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["s of these genes were verified by RT-qPCR on mouse disease model. Results: A total of 50 ARDEGs", "gulation of these hub inflammatory ARDEGs in mouse heart tissues. Conclusion: Aging-related gen", "aged male C57BL/6 mice (12 months old). The mice were obtained from the animal center of Xinjiang", "spital of Xinjiang Autonomous Region. 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