ArticleArteriosclerosis, thrombosis, and vascular biology2014
Cytochrome P450 2C8 ω3-long-chain polyunsaturated fatty acid metabolites increase mouse retinal pathologic neovascularization--brief report.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 51 citations in OpenAlex.
- Effect of fish oil on monoepoxides derived from fatty acids during cardiac surgery.Journal of lipid research · 2016Trial
- Regioselective epoxidation of a polyunsaturated fatty acid by a vanadyl complex with redox-active ligands.Chemical communications (Cambridge, England) · 2026Article
- Soluble Epoxide Hydrolase Inhibitors Improve Cornea Alkali Wound Healing.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Targeted lipidomics uncovers oxylipin perturbations and potential circulation biomarkers in Bietti's crystalline dystrophy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024Article
- Overexpression of soluble epoxide hydrolase reduces post-ischemic recovery of cardiac contractile function.Biochemical pharmacology · 2024Article
- Challenges and Opportunities in P450 Research on the Eye.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Beyond VEGF: Targeting Inflammation and Other Pathways for Treatment of Retinal Disease.The Journal of pharmacology and experimental therapeutics · 2023Review
- Decreased Expression of Soluble Epoxide Hydrolase Suppresses Murine Choroidal Neovascularization.International journal of molecular sciences · 2022Article
- Article
- Cytochrome P450 oxidase 2J inhibition suppresses choroidal neovascularization in mice.Metabolism: clinical and experimental · 2022Article
- Metabolomics and Biomarkers in Retinal and Choroidal Vascular Diseases.Metabolites · 2022Review
- Long-Chain Polyunsaturated Fatty Acids and Their Metabolites Regulate Inflammation in Age-Related Macular Degeneration.Journal of inflammation research · 2022Review
- Placental Angiogenesis in Mammals: A Review of the Regulatory Effects of Signaling Pathways and Functional Nutrients.Advances in nutrition (Bethesda, Md.) · 2021Review
- Effects of inflammation and soluble epoxide hydrolase inhibition on oxylipin composition of very low-density lipoproteins in isolated perfused rat livers.Physiological reports · 2021Article
- Eicosanoids and Oxidative Stress in Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2020Review
- A novel interaction between soluble epoxide hydrolase and the AT1 receptor in retinal microvascular damage.Prostaglandins & other lipid mediators · 2020Article
- Protective effect of Soluble Epoxide Hydrolase Inhibition in Retinal Vasculopathy associated with Polycystic Kidney Disease.Theranostics · 2020Article
- Soluble epoxide hydrolase promotes astrocyte survival in retinopathy of prematurity.The Journal of clinical investigation · 2019Article
- Dyslipidemia in retinal metabolic disorders.EMBO molecular medicine · 2019Review
- Soluble Epoxide Hydrolase Inhibition for Ocular Diseases: Vision for the Future.Frontiers in pharmacology · 2019Article
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveRegulation of angiogenesis is critical for many diseases. Specifically, pathological retinal neovascularization, a major cause of blindness, is suppressed with dietary ω3-long-chain polyunsaturated fatty acids (ω3LCPUFAs) through antiangiogenic metabolites of cyclooxygenase and lipoxygenase. Cytochrome P450 epoxygenases (CYP2C8) also metabolize LCPUFAs, producing bioactive epoxides, which are inactivated by soluble epoxide hydrolase (sEH) to transdihydrodiols. The effect of these enzymes and their metabolites on neovascularization is unknown. APPROACH AND
resultsThe mouse model of oxygen-induced retinopathy was used to investigate retinal neovascularization. We found that CYP2C (localized in wild-type monocytes/macrophages) is upregulated in oxygen-induced retinopathy, whereas sEH is suppressed, resulting in an increased retinal epoxide:diol ratio. With a ω3LCPUFA-enriched diet, retinal neovascularization increases in Tie2-driven human-CYP2C8-overexpressing mice (Tie2-CYP2C8-Tg), associated with increased plasma 19,20-epoxydocosapentaenoic acid and retinal epoxide:diol ratio. 19,20-Epoxydocosapentaenoic acids and the epoxide:diol ratio are decreased with overexpression of sEH (Tie2-sEH-Tg). Overexpression of CYP2C8 or sEH in mice does not change normal retinal vascular development compared with their wild-type littermate controls. The proangiogenic role in retina of CYP2C8 with both ω3LCPUFA and ω6LCPUFA and antiangiogenic role of sEH in ω3LCPUFA metabolism were corroborated in aortic ring assays.
conclusionsOur results suggest that CYP2C ω3LCPUFA metabolites promote retinal pathological angiogenesis. CYP2C8 is part of a novel lipid metabolic pathway influencing retinal neovascularization.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.