{"doi":"10.17615/f8bx-6k60","title":"Dual modulation of cyclooxygenase and CYP epoxygenase metabolism and acute vascular inflammation in mice","abstract":"Cyclooxygenase (COX)-derived prostaglandins and cytochrome P450 (CYP) epoxygenase-derived epoxyeicosatrienoic acids are important regulators of inflammation; however, functional interactions between these pathways in the regulation of vascular inflammation in vivo have not been studied. We investigated the relative and additive effects of endothelial CYP2J2 overexpression (Tie2-CYP2J2-Tr), global sEH disruption (Ephx2−/−), and pharmacologic COX inhibition with indomethacin on the acute vascular inflammatory response to endotoxin in mice. Compared to vehicle-treated wild-type C57BL/6 controls, induction of myeloperoxidase (MPO) activity in lung and liver was similarly attenuated in Tie2-CYP2J2-Tr mice, Ephx2−/− mice and wild-type mice treated with moderate dose indomethacin. Dual modulation of both pathways, however, did not produce an additive anti-inflammatory effect. These findings demonstrate that both COX and CYP epoxygenase-mediated eicosanoid metabolism are important regulators of the acute vascular inflammatory response in vivo, and suggest that the anti-inflammatory effects of modulating each pathway may be mediated, at least in part, by overlapping mechanisms.","journal":"UNC Libraries","year":2020,"id":142798,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9617,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":537497,"name":"Robert N. Schuck","orcid":"0000-0002-5855-1361","position":1,"is_corresponding":false},{"id":594279,"name":"Kimberly Molnar","orcid":null,"position":2,"is_corresponding":false},{"id":502251,"name":"Laura M. DeGraff","orcid":null,"position":3,"is_corresponding":false},{"id":247404,"name":"Darryl C. Zeldin","orcid":"0000-0002-2087-7307","position":4,"is_corresponding":false},{"id":241276,"name":"Fred B. Lih","orcid":"0000-0002-2260-816X","position":5,"is_corresponding":false},{"id":471243,"name":"Akinyemi Oni‐Orisan","orcid":"0000-0002-5897-5543","position":6,"is_corresponding":false},{"id":65890,"name":"Kenneth B. Tomer","orcid":null,"position":7,"is_corresponding":false},{"id":232872,"name":"Katherine N. Theken","orcid":"0000-0001-9918-9170","position":8,"is_corresponding":false},{"id":543431,"name":"Yangmei Deng","orcid":null,"position":9,"is_corresponding":false},{"id":323202,"name":"Matthew L. Edin","orcid":"0000-0002-7042-500X","position":10,"is_corresponding":false},{"id":232873,"name":"Craig R. Lee","orcid":"0000-0003-3595-5301","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:17:34.768426Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}