{"id":"2378e07a-0791-58e8-94db-094f1f73c321","stable_key":"c156003d-8cdf-5259-8561-9803795ecc82:mouse-dlat-kd-fao","predicate":"increases","statement":"Cardiac Dlat knockdown improved substrate-supported respiration in the two-hit HFpEF model.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"bd6b21ef-ac8c-574f-bbec-e435bc8e087b","mechanism_event_label":"mouse dlat kd fao","subject":{"id":"d3f48501-673f-562e-b48b-9a10f2b25237","slug":"mouse-dlat-knockdown","display_name":"Cardiomyocyte-targeted mouse Dlat shRNA knockdown","entity_type_key":"protein_state"},"object":{"id":"4277e9b5-6f0b-55b4-89b1-3201b6182f04","slug":"mouse-cardiac-fao","display_name":"Mouse cardiac fatty-acid oxidation capacity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"bd6b21ef-ac8c-574f-bbec-e435bc8e087b","stable_key":"c156003d-8cdf-5259-8561-9803795ecc82:mouse-dlat-kd-fao","event_type":"increases","label":"mouse dlat kd fao","description":"Model-specific finding; read linked claim context and source-access tier.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d3f48501-673f-562e-b48b-9a10f2b25237","slug":"mouse-dlat-knockdown","display_name":"Cardiomyocyte-targeted mouse Dlat shRNA knockdown","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"4277e9b5-6f0b-55b4-89b1-3201b6182f04","slug":"mouse-cardiac-fao","display_name":"Mouse cardiac fatty-acid oxidation capacity","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":"Two-hit model: 60% fat-calorie diet and L-NAME 0.5 g/L drinking water; vector dose not reported in reviewed text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"duration","value_text":"Two-hit protocol 15 weeks. Transgenic age/induction wording differs across passages; do not infer one exact interval","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"endpoint","value_text":"mouse-cardiac-fao","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"AAV9-cTnT-Dlat shRNA and Oroboros respirometry; Figure 5E–G","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":"mouse-dlat-knockdown","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. Partial knockdown, not complete deletion; not evidence that systemic DLAT inhibition is safe.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Cardiac Dlat knockdown improved substrate-supported respiration in the two-hit HFpEF model.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_locator","value_text":"[{\"cache\": \"artifacts/dlat-curation/heart-blocks.json\", \"block_index\": 40, \"text_sha256\": \"243609ee6c00a8f0af6ff98eb44fa8397862deb054738dfa97ffabdbb7be4763\", \"xml_element_id\": \"Par18\"}, {\"cache\": \"artifacts/dlat-curation/heart-blocks.json\", \"block_index\": 42, \"text_sha256\": \"6736653063633e10bc6238c895766205418e072440d0bb94d0415def1a9ec579\", \"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":"sample_size","value_text":"4 biological replicates","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":"7ee51e50-2539-549b-bd3e-f146c464d062","evidence_kind":"source_excerpt","locator":"Lines 406-421","start_line":406,"end_line":421,"excerpt":"Cardiac Dlat knockdown improved substrate-supported respiration in the two-hit HFpEF model.\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: Two-hit model: 60% fat-calorie diet and L-NAME 0.5 g/L drinking water; vector dose not reported in reviewed text\nduration: Two-hit protocol 15 weeks. Transgenic age/induction wording differs across passages; do not infer one exact interval\nprimary_references: https://doi.org/10.1038/s41467-026-70703-w\naccess_level: full_text_and_supplement_review\nevidence_location: AAV9-cTnT-Dlat shRNA and Oroboros respirometry; Figure 5E–G\nendpoint: mouse-cardiac-fao\nexposure: mouse-dlat-knockdown\nlimitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Partial knockdown, not complete deletion; not evidence that systemic DLAT inhibition is safe.\nprimary_locator: [{\"cache\": \"artifacts/dlat-curation/heart-blocks.json\", \"block_index\": 40, \"text_sha256\": \"243609ee6c00a8f0af6ff98eb44fa8397862deb054738dfa97ffabdbb7be4763\", \"xml_element_id\": \"Par18\"}, {\"cache\": \"artifacts/dlat-curation/heart-blocks.json\", \"block_index\": 42, \"text_sha256\": \"6736653063633e10bc6238c895766205418e072440d0bb94d0415def1a9ec579\", \"xml_element_id\": null}]\nplain_language: Cardiac Dlat knockdown improved substrate-supported respiration in the two-hit HFpEF model.\nsample_size: 4 biological replicates","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}