Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36726122", "kind": "science-record", "revision": 4, "content_hash": "sha256:18388561569ce6291f895c0e95ad62182e80bd5845c46814ba5f8d07e741bf90", "created_at": "2026-11-01T19:01:17Z", "updated_at": "2026-11-01T22:51:09Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis.", "doi": "10.1186/s12967-023-03928-8", "pmid": "36726122", "authors": ["Cheng Peng", "Yanxiu Zhang", "Xueyan Lang", "Yao Zhang"], "journal": "Journal of translational medicine", "year": 2023, "abstract": "BACKGROUND: Diabetic cardiomyopathy (DCM) is one of the common cardiovascular complications of diabetes and a leading cause of death in diabetic patients. Mitochondrial metabolism and immune-inflammation are key for DCM pathogenesis, but their crosstalk in DCM remains an open issue. This study explored the separate roles of mitochondrial metabolism and immune microenvironment and their crosstalk in DCM with bioinformatics.\nMETHODS: DCM chip data (GSE4745, GSE5606, and GSE6880) were obtained from NCBI GEO, while mitochondrial gene data were downloaded from MitoCarta3.0 database. Differentially expressed genes (DEGs) were screened by GEO2R and processed for GSEA, GO and KEGG pathway analyses. Mitochondria-related DEGs (MitoDEGs) were obtained. A PPI network was constructed, and the hub MitoDEGs closely linked to DCM or heart failure were identified with CytoHubba, MCODE and CTD scores. Transcription factors and target miRNAs of the hub MitoDEGs were predicted with Cytoscape and miRWalk database, respectively, and a regulatory network was established. The immune infiltration pattern in DCM was analyzed with ImmuCellAI, while the relationship between MitoDEGs and immune infiltration abundance was investigated using Spearman method. A rat model of DCM was established to validate the expression of hub MitoDEGs and their relationship with cardiac function.\nRESULTS: MitoDEGs in DCM were significantly enriched in pathways involved in mitochondrial metabolism, immunoregulation, and collagen synthesis. Nine hub MitoDEGs closely linked to DCM or heart failure were obtained. Immune analysis revealed significantly increased infiltration of B cells while decreased infiltration of DCs in immune microenvironment of DCM. Spearman analysis demonstrated that the hub MitoDEGs were positively associated with the infiltration of pro-inflammatory immune cells, but negatively associated with the infiltration of anti-inflammatory or regulatory immune cells. In the animal experiment, 4 hub MitoDEGs (Pdk4, Hmgcs2, Decr1, and Ivd) showed an expression trend consistent with bioinformatics analysis result. Additionally, the up-regulation of Pdk4, Hmgcs2, Decr1 and the down-regulation of Ivd were distinctly linked to reduced cardiac function.\nCONCLUSIONS: This study unraveled the interaction between mitochondrial metabolism and immune microenvironment in DCM, providing new insights into the research on potential pathogenesis of DCM and the exploration of novel targets for medical interventions.", "claims": [{"id": "claim-method", "statement": "DEGs from each microarray were obtained with R package \"limma\" as implemented by GEO2R online tool (https://www.ncbi.nlm.nih.gov/geo/geo2r/) [26], and all identified DEGs met p < 0.05 and |log2 (Fold-change)|≥ 1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36726122", "locator": "sections[4] \"Acquisition of microarray data and identification of differentially expressed genes (DEGs)\" paragraph 2", "quote": "DEGs from each microarray were obtained with R package \"limma\" as implemented by GEO2R online tool (https://www.ncbi.nlm.nih.gov/geo/geo2r/) [26], and all identified DEGs met p < 0.05 and |log2 (Fold-change)|≥ 1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analysed during the current study are available in the GEO database (https://www.ncbi.nlm.nih.gov/geo/)and MitoCarta3.0 (http://www.broadinstitute.org/mitocarta), which is an updating, openly available for free download, authoritative database of mitochondrial proteome including sub-mitochondrial localization and MitoPathway annotations.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36726122", "locator": "sections[38] \"notes\" paragraph 1", "quote": "The datasets analysed during the current study are available in the GEO database (https://www.ncbi.nlm.nih.gov/geo/)and MitoCarta3.0 (http://www.broadinstitute.org/mitocarta), which is an updating, openly available for free download, authoritative database of mitochondrial proteome including sub-mitochondrial localization and MitoPathway annotations."}], "state": "complete"}, {"id": "claim-target-result", "statement": "MitoDEGs in DCM were significantly enriched in pathways involved in mitochondrial metabolism, immunoregulation, and collagen synthesis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36726122", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "MitoDEGs in DCM were significantly enriched in pathways involved in mitochondrial metabolism, immunoregulation, and collagen synthesis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "MitoDEGs in DCM were significantly enriched in pathways involved in mitochondrial metabolism, immunoregulation, and collagen synthesis.", "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:36726122"], "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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A rat model of DCM was established to validate the", "d with a low-dose STZ injection [41–43]. The rats were allowed to acclimate for 1 week with free ac", "h/12 h light/dark cycle. Following that, the rats were divided into the CON and DCM groups by rando", "kg, Solarbio) was intraperitoneally injected in rats of the DCM group to induce T2DM, and citric"], "order_basis": "paper_text_order:1341", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["r1 and Ivd between the DCM and CON groups by western blotting and immunohistochemistry. 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