{"id":"3566581f-9220-531d-bfd4-2fe700f0e56d","stable_key":"c156003d-8cdf-5259-8561-9803795ecc82:spd-function","predicate":"reduces","statement":"Spermidine improved the reported diastolic phenotype of mice in the HFpEF experiment.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"19a1134d-96f4-5e92-8384-404ce4fb8773","mechanism_event_label":"spd function","subject":{"id":"7014993c-468f-5c6b-ab04-80c87f9dfd9f","slug":"spermidine","display_name":"Spermidine","entity_type_key":"small_molecule"},"object":{"id":"2ece61c9-ca48-516e-b637-db426cde0da3","slug":"mouse-cardiac-diastolic-impairment","display_name":"Mouse cardiac diastolic impairment","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"19a1134d-96f4-5e92-8384-404ce4fb8773","stable_key":"c156003d-8cdf-5259-8561-9803795ecc82:spd-function","event_type":"reduces","label":"spd function","description":"Model-specific finding; read linked claim context and source-access tier.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7014993c-468f-5c6b-ab04-80c87f9dfd9f","slug":"spermidine","display_name":"Spermidine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2ece61c9-ca48-516e-b637-db426cde0da3","slug":"mouse-cardiac-diastolic-impairment","display_name":"Mouse cardiac diastolic impairment","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"access_level","value_text":"full_text_and_supplement_review","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"compartment","value_text":"Cardiac tissue / mitochondria","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"dose","value_text":"30 mM drinking water","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"duration","value_text":"10 weeks in Results","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"endpoint","value_text":"mouse-cardiac-diastolic-impairment","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Figure 8H–K; Supplementary Figure S24","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"spermidine","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. HADHA necessity for this systemic intervention was not established by a genetic blocking experiment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Topical cross-reference only; no inheritance of another actor's effects.","comparator":null,"unit":null,"notes":"","entity":{"slug":"spermidine","display_name":"Spermidine","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Spermidine improved the reported diastolic phenotype of mice in the HFpEF experiment.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_locator","value_text":"[{\"cache\": \"artifacts/dlat-curation/heart-blocks.json\", \"block_index\": 54, \"text_sha256\": \"ecfe210aa0338ec52935a354f2bcc46289d65981b7b09fd4299e4e4f2fac4254\", \"xml_element_id\": \"Par22\"}, {\"cache\": \"artifacts/dlat-curation/heart-blocks.json\", \"block_index\": 56, \"text_sha256\": \"b4baf8321f41630eff2d66a4181f2907f674041d430ba7878fd278f33d4141cf\", \"xml_element_id\": null}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"https://doi.org/10.1038/s41467-026-70703-w","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"Drinking water","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"sample_size","value_text":"8 per group","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cardiac tissue and cardiomyocytes","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"4adec6a3-a8b7-52ca-8988-000e2a2d0d92","evidence_kind":"source_excerpt","locator":"Lines 679-695","start_line":679,"end_line":695,"excerpt":"Spermidine improved the reported diastolic phenotype of mice in the HFpEF experiment.\norganism: Mus musculus\ntissue_or_cell_type: Cardiac tissue and cardiomyocytes\nexperimental_model: Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated\ncompartment: Cardiac tissue / mitochondria\ndose: 30 mM drinking water\nduration: 10 weeks in Results\nroute: Drinking water\nprimary_references: https://doi.org/10.1038/s41467-026-70703-w\naccess_level: full_text_and_supplement_review\nevidence_location: Figure 8H–K; Supplementary Figure S24\nendpoint: mouse-cardiac-diastolic-impairment\nexposure: spermidine\nlimitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. HADHA necessity for this systemic intervention was not established by a genetic blocking experiment.\nprimary_locator: [{\"cache\": \"artifacts/dlat-curation/heart-blocks.json\", \"block_index\": 54, \"text_sha256\": \"ecfe210aa0338ec52935a354f2bcc46289d65981b7b09fd4299e4e4f2fac4254\", \"xml_element_id\": \"Par22\"}, {\"cache\": \"artifacts/dlat-curation/heart-blocks.json\", \"block_index\": 56, \"text_sha256\": \"b4baf8321f41630eff2d66a4181f2907f674041d430ba7878fd278f33d4141cf\", \"xml_element_id\": null}]\nplain_language: Spermidine improved the reported diastolic phenotype of mice in the HFpEF experiment.\nsample_size: 8 per group","model_system":"Mouse two-hit HFpEF model: 60% fat-calorie diet plus L-NAME 0.5 g/L drinking water; additional intervention as stated","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Quotation is the authored curation, not original publisher wording. Exact primary locators and access limits retained in contexts.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"ee72956d-4fd4-58d3-9a94-e173bb1e3282","stable_key":"import-c156003d-8cdf-5259-8561-9803795ecc82","title":"DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence","document_type":"imported_text","citation_label":"AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation.","file_path":"","sha256":"159e5472c8b1d104625f9c648dc9ee24dcd5fe102109fd960bba50e9ba9de954","revision_id":"5ca6b1f1-fd75-5f8d-ba2b-0215fbf387c7","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}