{"id":"b3939fa5-bcc6-5e3b-844d-2401551725b6","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:nia-clin-4py-mouse-vcam","predicate":"induces_in_mouse_experiment","statement":"Physiological-level 4PY exposure, unlike structural isomer 2PY, induced vascular VCAM-1 expression and leukocyte adherence in mice.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"ba994792-ed59-5589-9703-ac0ae9cd6673","mechanism_event_label":"In mice, one breakdown product directly promoted a vessel-wall adhesion response; its close chemical relative did not.","subject":{"id":"257094c9-2e70-5e55-9831-7d04d73dcb85","slug":"n1-methyl-4-pyridone-3-carboxamide","display_name":"N1-methyl-4-pyridone-3-carboxamide (4PY)","entity_type_key":"small_molecule"},"object":{"id":"8e989f28-9495-5686-a77e-853ce0a1d522","slug":"mouse-endothelial-vcam1-expression","display_name":"Mouse endothelial Vcam1 expression","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ba994792-ed59-5589-9703-ac0ae9cd6673","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:nia-clin-4py-mouse-vcam-event","event_type":"biochemical_relationship","label":"In mice, one breakdown product directly promoted a vessel-wall adhesion response; its close chemical relative did not.","description":"Physiological-level 4PY exposure, unlike structural isomer 2PY, induced vascular VCAM-1 expression and leukocyte adherence in mice.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"26d3c59a-5ba8-50c6-8fb0-654cc6b6c8a6","slug":"mouse-vcam1","display_name":"Mouse vascular cell adhesion molecule 1 / Vcam1","entity_type_key":"protein"},"role":"induced_protein","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"85f62bfc-b7ab-5096-8ef0-16c54983b7d6","slug":"endothelial-leukocyte-adhesion","display_name":"Leukocyte adherence to vascular endothelium","entity_type_key":"cellular_process"},"role":"measured_consequence","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"d462430c-2f74-56ad-abf6-d1872c4f83a1","slug":"n1-methyl-2-pyridone-5-carboxamide","display_name":"N1-methyl-2-pyridone-5-carboxamide (2PY)","entity_type_key":"small_molecule"},"role":"negative_comparator","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"257094c9-2e70-5e55-9831-7d04d73dcb85","slug":"n1-methyl-4-pyridone-3-carboxamide","display_name":"N1-methyl-4-pyridone-3-carboxamide (4PY)","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"8e989f28-9495-5686-a77e-853ce0a1d522","slug":"mouse-endothelial-vcam1-expression","display_name":"Mouse endothelial Vcam1 expression","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Mouse vascular cell adhesion molecule 1 / Vcam1 (induced_protein); Leukocyte adherence to vascular endothelium (measured_consequence); N1-methyl-2-pyridone-5-carboxamide (2PY) (negative_comparator)","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/niacin-clinical-sources/ferrell2024.abstract.txt\", \"locator\": \"Indexed primary abstract\", \"file_sha256\": \"09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19\", \"start_char\": 0, \"end_char\": 2066, \"text_sha256\": \"09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Prospective cardiac cohorts, genetic associations, and separate mouse metabolite exposures","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Discovery cohort 1,162; US validation 2,331 and European validation 832; three-year cardiovascular follow-up; physiological-level mouse metabolite exposure","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Human metabolite associations are not randomized effects of niacin intake. Renal handling and other determinants of levels matter. Mouse exposure results do not prove dietary niacin or supplements caused human events.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Niacin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"niacin","display_name":"Niacin (vitamin B3)","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"In mice, one breakdown product directly promoted a vessel-wall adhesion response; its close chemical relative did not.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[nia-clin-ferrell2024] A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. (2024). https://pubmed.ncbi.nlm.nih.gov/38374343/ DOI: 10.1038/s41591-023-02793-8","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Circulating metabolites and mouse vascular endothelium","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"f5eaeea2-598a-5aca-9741-7b138e928373","evidence_kind":"source_excerpt","locator":"Lines 1585-1597","start_line":1585,"end_line":1597,"excerpt":"### nia-clin-4py-mouse-vcam\nPhysiological-level 4PY exposure, unlike structural isomer 2PY, induced vascular VCAM-1 expression and leukocyte adherence in mice.\nCondition category: normal\nnutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: In mice, one breakdown product directly promoted a vessel-wall adhesion response; its close chemical relative did not.\norganism: Mus musculus\ntissue_or_cell_type: Circulating metabolites and mouse vascular endothelium\nexperimental_model: Prospective cardiac cohorts, genetic associations, and separate mouse metabolite exposures\nlimitations: Human metabolite associations are not randomized effects of niacin intake. Renal handling and other determinants of levels matter. Mouse exposure results do not prove dietary niacin or supplements caused human events.\nexposure: Discovery cohort 1,162; US validation 2,331 and European validation 832; three-year cardiovascular follow-up; physiological-level mouse metabolite exposure\ncross_nutrient: Mouse vascular cell adhesion molecule 1 / Vcam1 (induced_protein); Leukocyte adherence to vascular endothelium (measured_consequence); N1-methyl-2-pyridone-5-carboxamide (2PY) (negative_comparator)\nevidence_span: {\"source_cache\": \"artifacts/niacin-clinical-sources/ferrell2024.abstract.txt\", \"locator\": \"Indexed primary abstract\", \"file_sha256\": \"09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19\", \"start_char\": 0, \"end_char\": 2066, \"text_sha256\": \"09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19\"}\n[nia-clin-ferrell2024] A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. (2024). https://pubmed.ncbi.nlm.nih.gov/38374343/ DOI: 10.1038/s41591-023-02793-8","model_system":"Prospective cardiac cohorts, genetic associations, and separate mouse metabolite exposures","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [nia-clin-ferrell2024] A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. (2024). https://pubmed.ncbi.nlm.nih.gov/38374343/ DOI: 10.1038/s41591-023-02793-8","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"a62b7b5b-786a-57e9-85e9-67c6912a5054","stable_key":"import-a9dd23c6-978a-5755-8bd8-f29bd1fe0cda","title":"Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. 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