{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:17:59Z","timestamp":1790957879443,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Pathological ocular neovascularization is a major cause of blindness. Increased dietary intake of \u03c9-3 long-chain polyunsaturated fatty acids (LCPUFA) reduces retinal neovascularization and choroidal neovascularization (CNV), but \u03c9-3 LCPUFA metabolites of a major metabolizing pathway, cytochrome P450 oxidase (CYP) 2C, promote ocular pathological angiogenesis. We hypothesized that inhibition of CYP2C activity will add to the protective effects of \u03c9-3 LCPUFA on neovascular eye diseases.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>The mouse models of oxygen-induced retinopathy and laser-induced CNV were used to investigate pathological angiogenesis in the retina and choroid, respectively. The plasma levels of \u03c9-3 LCPUFA metabolites of CYP2C were determined by mass spectroscopy. Aortic ring and choroidal explant sprouting assays were used to investigate the effects of CYP2C inhibition and \u03c9-3 LCPUFA\u2013derived CYP2C metabolic products on angiogenesis ex vivo. We found that inhibition of CYP2C activity by montelukast added to the protective effects of \u03c9-3 LCPUFA on retinal neovascularization and CNV by 30% and 20%, respectively. In CYP2C8-overexpressing mice fed a \u03c9-3 LCPUFA diet, montelukast suppressed retinal neovascularization and CNV by 36% and 39% and reduced the plasma levels of CYP2C8 products. Soluble epoxide hydrolase inhibition, which blocks breakdown and inactivation of CYP2C \u03c9-3 LCPUFA\u2013derived active metabolites, increased oxygen-induced retinopathy and CNV in vivo. Exposure to selected \u03c9-3 LCPUFA metabolites of CYP2C significantly reversed the suppression of both angiogenesis ex vivo and endothelial cell functions in vitro by the CYP2C inhibitor montelukast.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Inhibition of CYP2C activity adds to the protective effects of \u03c9-3 LCPUFA on pathological retinal neovascularization and CNV.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.116.307558","type":"journal-article","created":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T03:14:36Z","timestamp":1468552476000},"page":"1919-1927","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":45,"title":["Cytochrome P450 Oxidase 2C Inhibition Adds to \u03c9-3 Long-Chain Polyunsaturated Fatty Acids Protection Against Retinal and Choroidal Neovascularization"],"prefix":"10.1161","volume":"36","author":[{"given":"Yan","family":"Gong","sequence":"first","affiliation":[{"name":"From the Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School, MA (Y.G., Z.F., C.-H.L., Z.W., Z.S., T.W.F., N.J.S., P.C.M., S.B.B., S.S.M., E.P.M., L.E.H.S.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (M.L.E., F.B.L., D.C.Z.); Department of Entomology and Comprehensive Cancer Center, University of California, Davis (K.S.S.L., B.D.H.); Section on Nutritional Neurosciences..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongjie","family":"Fu","sequence":"additional","affiliation":[{"name":"From the Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School, MA (Y.G., Z.F., C.-H.L., Z.W., Z.S., T.W.F., N.J.S., P.C.M., S.B.B., S.S.M., E.P.M., L.E.H.S.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (M.L.E., F.B.L., D.C.Z.); Department of Entomology and Comprehensive Cancer Center, University of California, Davis (K.S.S.L., B.D.H.); Section on Nutritional Neurosciences..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew L.","family":"Edin","sequence":"additional","affiliation":[{"name":"From the Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School, MA (Y.G., Z.F., C.-H.L., Z.W., Z.S., T.W.F., N.J.S., P.C.M., S.B.B., S.S.M., E.P.M., L.E.H.S.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (M.L.E., F.B.L., D.C.Z.); Department of Entomology and Comprehensive Cancer Center, University of California, Davis (K.S.S.L., B.D.H.); Section on Nutritional Neurosciences..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Hsiu","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School, MA (Y.G., Z.F., C.-H.L., Z.W., Z.S., T.W.F., N.J.S., P.C.M., S.B.B., S.S.M., E.P.M., L.E.H.S.); Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (M.L.E., F.B.L., D.C.Z.); Department of Entomology and Comprehensive Cancer Center, University of California, Davis (K.S.S.L., B.D.H.); Section on Nutritional Neurosciences..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxiao","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School, MA (Y.G., Z.F., C.-H.L., Z.W., Z.S., T.W.F., N.J.S., P.C.M., S.B.B., S.S.M., E.P.M., L.E.H.S.); 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