CACNB4 attenuates cardiac dysfunction by regulating calcium and ATP levels via interaction with RyR2.

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We analyzed gene expression profiles of peripheral blood mononuclear cells (PBMCs) from heart failure patients using the GSE235757 data set from the NCBI GEO database. KEGG enrichment analysis was performed to identify pathways associated with differentially expressed genes. Analysis of the GSE235757 data set revealed a significant downregulation of CACNB4 expression in PBMCs of heart failure patients, particularly in the \"Cardiac muscle contraction\" pathway. Western blot analysis confirmed a reduction in CACNB4 expression in hypoxic myocardial cells and heart tissue from heart failure mice. Overexpression of CACNB4 improved cardiac function, reduced infarct size, alleviated myocardial damage, via enhancing ATP and Ca2+ levels. Further analysis identified an interaction between CACNB4 and RyR2, which improve Ca2+ and ATP levels. This study demonstrated that CACNB4 interacts with RyR2 to regulate intracellular Ca2+ and ATP levels, which are critical for maintaining cardiac function.", "claims": [{"id": "claim-method", "statement": "Measurement data were compared using the t test and presented as mean ± standard deviation (SD).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41194296", "locator": "sections[15] \"Statistical analysis\" paragraph 2", "quote": "Measurement data were compared using the t test and presented as mean ± standard deviation (SD)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analysed during the current study are available in the GEO repository (GSE235757).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41194296", "locator": "sections[27] \"Data availability\" paragraph 2", "quote": "The datasets generated and/or analysed during the current study are available in the GEO repository (GSE235757)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "This study demonstrated that CACNB4 interacts with RyR2 to regulate intracellular Ca2+ and ATP levels, which are critical for maintaining cardiac function.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41194296", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "This study demonstrated that CACNB4 interacts with RyR2 to regulate intracellular Ca2+ and ATP levels, which are critical for maintaining cardiac function."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "This study demonstrated that CACNB4 interacts with RyR2 to regulate intracellular Ca2+ and ATP levels, which are critical for maintaining cardiac function.", "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:41194296"], "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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