{"id":"57a0376f-c061-51ae-8ab3-0f44701c0b3c","stable_key":"1fb6218a-60d1-55ea-87fe-07d15d0fc46f:ggpp-reverses-the-nos-response","predicate":"reduces","statement":"Geranylgeranyl diphosphate reversed the statin-induced rise in endothelial nitric oxide synthase, while farnesyl diphosphate and low-density lipoprotein did not.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"4fc42713-a53b-5871-ab4a-2d7c7d47ad33","mechanism_event_label":"Geranylgeranyl diphosphate reversed the statin-induced rise in endothelial nitric oxide synthase, while farnesyl diphosphate and low-density lipoprotein did not.","subject":{"id":"7e6d85c1-25b7-549b-9883-8e9d5d11ae3d","slug":"geranylgeranyl-diphosphate","display_name":"Geranylgeranyl diphosphate / GGPP","entity_type_key":"small_molecule"},"object":{"id":"8a9c57f6-eafd-5243-afaf-d4e830939c4b","slug":"nos3","display_name":"Human endothelial nitric oxide synthase / eNOS / NOS3","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"4fc42713-a53b-5871-ab4a-2d7c7d47ad33","stable_key":"1fb6218a-60d1-55ea-87fe-07d15d0fc46f:ggpp-reverses-the-nos-response-event","event_type":"observed_relationship","label":"Geranylgeranyl diphosphate reversed the statin-induced rise in endothelial nitric oxide synthase, while farnesyl diphosphate and low-density lipoprotein did not.","description":"Geranylgeranyl diphosphate reversed the statin-induced rise in endothelial nitric oxide synthase, while farnesyl diphosphate and low-density lipoprotein did not.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"7e6d85c1-25b7-549b-9883-8e9d5d11ae3d","slug":"geranylgeranyl-diphosphate","display_name":"Geranylgeranyl diphosphate / GGPP","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8a9c57f6-eafd-5243-afaf-d4e830939c4b","slug":"nos3","display_name":"Human endothelial nitric oxide synthase / eNOS / NOS3","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"aa3152b9-b04f-5a0d-bf87-e9c1dbe0e1f9","slug":"mevastatin","display_name":"Mevastatin","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"9ccdf853-7005-5a53-b053-83574a870ad7","slug":"farnesyl-diphosphate","display_name":"Farnesyl diphosphate / FPP","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Not stated here","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human endothelial cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Geranylgeranyl diphosphate 1 to 10 micromolar, farnesyl diphosphate 5 to 10 micromolar, L-mevalonate 200 micromolar or LDL 1 mg/ml added with mevastatin","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This identifies which isoprenoid carries the effect; it does not establish that geranylgeranyl diphosphate is limiting at ordinary statin doses in a person.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Human endothelial cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Geranylgeranyl diphosphate reversed the statin-induced rise in endothelial nitric oxide synthase, while farnesyl diphosphate and low-density lipoprotein did not.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. (1998). https://pubmed.ncbi.nlm.nih.gov/9727051/ DOI: 10.1074/jbc.273.37.24266","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vitro","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Endothelial nitric oxide synthase expression and Rho membrane translocation","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"1e7b49c2-4f5e-5fd7-b4df-ae50fd8ab6cd","evidence_kind":"source_excerpt","locator":"Lines 67-76","start_line":67,"end_line":76,"excerpt":"## ggpp-reverses-the-nos-response\nGeranylgeranyl diphosphate reversed the statin-induced rise in endothelial nitric oxide synthase, while farnesyl diphosphate and low-density lipoprotein did not.\nModel/species: Human endothelial cells\nTissue/system: Endothelial nitric oxide synthase expression and Rho membrane translocation\nExposure: Geranylgeranyl diphosphate 1 to 10 micromolar, farnesyl diphosphate 5 to 10 micromolar, L-mevalonate 200 micromolar or LDL 1 mg/ml added with mevastatin\nRoute: In vitro\nDuration: Not stated here\nLimits: This identifies which isoprenoid carries the effect; it does not establish that geranylgeranyl diphosphate is limiting at ordinary statin doses in a person.\nPrimary reference: Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. (1998). https://pubmed.ncbi.nlm.nih.gov/9727051/ DOI: 10.1074/jbc.273.37.24266\nAccess: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","model_system":"","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"a4431d8c-34d7-5db7-9edf-a35f68feba39","stable_key":"import-1fb6218a-60d1-55ea-87fe-07d15d0fc46f","title":"Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twelve primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Findings obtained with mevastatin, simvastatin or the statin class are recorded against those subjects. Study-specific citations, doses, negative findings and limitations retained. Not publisher full text.","file_path":"","sha256":"6307f1acf99f90662320328974781ee660348754257b1e1555701ad597edc8e5","revision_id":"447c5978-ba3f-58fe-ac85-664caa72e01b","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}