{"id":"66c3f8e5-cbcc-52d1-b5e5-c21e700b8c9f","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:ver-endo-combined-e-gpx4-loss","predicate":"increases","statement":"Six weeks of vitamin E-depleted diet before inducible endothelial Gpx4 deletion led to endothelial detachment and cell death in multiple mouse organs, accompanied by thrombosis and approximately 80% knockout mortality.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"cfc1149b-8de4-578d-a5d2-13382bb6ac42","mechanism_event_label":"Removing dietary vitamin E exposed severe vascular injury in mice whose endothelial GPX4 was then deleted.","subject":{"id":"08b2e09d-0fa9-56b8-b723-801569bf3f2f","slug":"gpx4-endothelial-loss","display_name":"Endothelium-directed GPX4 loss","entity_type_key":"protein_state"},"object":{"id":"1a3ea54c-e548-5c3c-bcec-8170c93b9d4b","slug":"endothelial-cell-death","display_name":"Endothelial cell death","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"cfc1149b-8de4-578d-a5d2-13382bb6ac42","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:ver-endo-combined-e-gpx4-loss-event","event_type":"biochemical_relationship","label":"Removing dietary vitamin E exposed severe vascular injury in mice whose endothelial GPX4 was then deleted.","description":"Six weeks of vitamin E-depleted diet before inducible endothelial Gpx4 deletion led to endothelial detachment and cell death in multiple mouse organs, accompanied by thrombosis and approximately 80% knockout mortality.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"40a6525a-76b8-576e-b73d-1e11aecf5f8d","slug":"alpha-tocopherol","display_name":"Alpha-tocopherol","entity_type_key":"small_molecule"},"role":"depleted nutrient","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e9bb13ee-f238-51e6-9101-78ddfd11465c","slug":"gpx4","display_name":"GPX4","entity_type_key":"protein"},"role":"deleted enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"08b2e09d-0fa9-56b8-b723-801569bf3f2f","slug":"gpx4-endothelial-loss","display_name":"Endothelium-directed GPX4 loss","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"1a3ea54c-e548-5c3c-bcec-8170c93b9d4b","slug":"endothelial-cell-death","display_name":"Endothelial cell death","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Combined dietary depletion and 4-hydroxytamoxifen-induced deletion","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Six-week vitamin E depletion preceding Gpx4 deletion.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Primary abstract only; vascular and survival endpoints in one mouse deletion model, not general human deficiency or dosing evidence.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin E research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-e","display_name":"Vitamin E","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Removing dietary vitamin E exposed severe vascular injury in mice whose endothelial GPX4 was then deleted.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ver-wortmann2013] Combined deficiency in glutathione peroxidase 4 and vitamin E causes multiorgan thrombus formation and early death in mice. (2013). https://pubmed.ncbi.nlm.nih.gov/23770613/ DOI: 10.1161/circresaha.113.279984","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Multiorgan vascular endothelium","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"e8299f94-6bf5-5df0-a223-50985fadcec0","evidence_kind":"source_excerpt","locator":"Lines 648-660","start_line":648,"end_line":660,"excerpt":"### ver-endo-combined-e-gpx4-loss\nSix weeks of vitamin E-depleted diet before inducible endothelial Gpx4 deletion led to endothelial detachment and cell death in multiple mouse organs, accompanied by thrombosis and approximately 80% knockout mortality.\nCondition category: nutrient_deficiency\nnutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Removing dietary vitamin E exposed severe vascular injury in mice whose endothelial GPX4 was then deleted.\norganism: Mus musculus\ntissue_or_cell_type: Multiorgan vascular endothelium\nexperimental_model: Combined dietary depletion and 4-hydroxytamoxifen-induced deletion\nlimitations: Primary abstract only; vascular and survival endpoints in one mouse deletion model, not general human deficiency or dosing evidence.\nexposure: Six-week vitamin E depletion preceding Gpx4 deletion.\ncross_nutrient: true\nevidence_location: Primary abstract\n[ver-wortmann2013] Combined deficiency in glutathione peroxidase 4 and vitamin E causes multiorgan thrombus formation and early death in mice. 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