Canagliflozin mitigates ferroptosis and ameliorates heart failure in rats with preserved ejection fraction.

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But, the underlying mechanisms remain unclear, particularly its effects on ferroptosis, a newly defined mechanism of iron-dependent non-apoptotic cell death during heart failure (HF). Here, with proteomics, we demonstrated that ferroptosis might be a key mechanism in a rat model of high-salt diet-induced HFpEF, characterized by iron overloading and lipid peroxidation, which was blocked following treatment with canagliflozin. Data are available via ProteomeXchange with identifier PXD029031. The ferroptosis was evaluated with the levels of acyl-CoA synthetase long-chain family member 4, glutathione peroxidase 4, ferritin heavy chain 1, transferrin receptor, Ferroportin 1, iron, glutathione, malondialdehyde, and 4-hydroxy-trans-2-nonenal. These findings highlight the fact that targeting ferroptosis may serve as a cardioprotective strategy for HFpEF prevention and suggest that canagliflozin may exert its cardiovascular benefits partly via its mitigation of ferroptosis.", "claims": [{"id": "claim-method", "statement": "Statistical comparisons were performed using one-way ANOVA followed by Bonferroni’s multiple comparison test or Tamhane’s multiple comparison test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35476142", "locator": "sections[18] \"Statistical analysis\" paragraph 2", "quote": "Statistical comparisons were performed using one-way ANOVA followed by Bonferroni’s multiple comparison test or Tamhane’s multiple comparison test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data for this research work were made available at submission.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35476142", "locator": "sections[32] \"notes\" paragraph 1", "quote": "Data for this research work were made available at submission."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Here, with proteomics, we demonstrated that ferroptosis might be a key mechanism in a rat model of high-salt diet-induced HFpEF, characterized by iron overloading and lipid peroxidation, which was blocked following treatment with canagliflozin.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35476142", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Here, with proteomics, we demonstrated that ferroptosis might be a key mechanism in a rat model of high-salt diet-induced HFpEF, characterized by iron overloading and lipid peroxidation, which was blocked following treatment with canagliflozin."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Here, with proteomics, we demonstrated that ferroptosis might be a key mechanism in a rat model of high-salt diet-induced HFpEF, characterized by iron overloading and lipid peroxidation, which was blocked following treatment with canagliflozin.", "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:35476142"], "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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