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Therapeutic potential of omega-3 fatty acid-derived epoxyeicosanoids in cardiovascular and inflammatory diseases.
Pharmacol Ther 2018; 183:177-204P&T

Abstract

Numerous benefits have been attributed to dietary long-chain omega-3 polyunsaturated fatty acids (n-3 LC-PUFAs), including protection against cardiac arrhythmia, triglyceride-lowering, amelioration of inflammatory, and neurodegenerative disorders. This review covers recent findings indicating that a variety of these beneficial effects are mediated by "omega-3 epoxyeicosanoids", a class of novel n-3 LC-PUFA-derived lipid mediators, which are generated via the cytochrome P450 (CYP) epoxygenase pathway. CYP enzymes, previously identified as arachidonic acid (20:4n-6; AA) epoxygenases, accept eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3; DHA), the major fish oil n-3 LC-PUFAs, as efficient alternative substrates. In humans and rodents, dietary EPA/DHA supplementation causes a profound shift of the endogenous CYP-eicosanoid profile from AA- to EPA- and DHA-derived metabolites, increasing, in particular, the plasma and tissue levels of 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP). Based on preclinical studies, these omega-3 epoxyeicosanoids display cardioprotective, vasodilatory, anti-inflammatory, and anti-allergic properties that contribute to the beneficial effects of n-3 LC-PUFAs in diverse disease conditions ranging from cardiac disease, bronchial disorders, and intraocular neovascularization, to allergic intestinal inflammation and inflammatory pain. Increasing evidence also suggests that background nutrition as well as genetic and disease state-related factors could limit the response to EPA/DHA-supplementation by reducing the formation and/or enhancing the degradation of omega-3 epoxyeicosanoids. Recently, metabolically robust synthetic analogs mimicking the biological activities of 17,18-EEQ have been developed. These drug candidates may overcome limitations of dietary EPA/DHA supplementation and provide novel options for the treatment of cardiovascular and inflammatory diseases.

Authors+Show Affiliations

Max Delbrueck Center for Molecular Medicine, Berlin, Germany. Electronic address: schunck@mdc-berlin.de.OMEICOS Therapeutics GmbH, Berlin, Germany.OMEICOS Therapeutics GmbH, Berlin, Germany.Department of Gastroenterology, Diabetes, Oncology and Rheumatology, Ruppiner Kliniken, Brandenburg Medical School, Neuruppin, Germany; Lipid Clinic, Experimental and Clinical Research Centre (ECRC), Charité University Medicine and Max Delbrueck Center for Molecular Medicine, Berlin, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

29080699

Citation

Schunck, Wolf-Hagen, et al. "Therapeutic Potential of Omega-3 Fatty Acid-derived Epoxyeicosanoids in Cardiovascular and Inflammatory Diseases." Pharmacology & Therapeutics, vol. 183, 2018, pp. 177-204.
Schunck WH, Konkel A, Fischer R, et al. Therapeutic potential of omega-3 fatty acid-derived epoxyeicosanoids in cardiovascular and inflammatory diseases. Pharmacol Ther. 2018;183:177-204.
Schunck, W. H., Konkel, A., Fischer, R., & Weylandt, K. H. (2018). Therapeutic potential of omega-3 fatty acid-derived epoxyeicosanoids in cardiovascular and inflammatory diseases. Pharmacology & Therapeutics, 183, pp. 177-204. doi:10.1016/j.pharmthera.2017.10.016.
Schunck WH, et al. Therapeutic Potential of Omega-3 Fatty Acid-derived Epoxyeicosanoids in Cardiovascular and Inflammatory Diseases. Pharmacol Ther. 2018;183:177-204. PubMed PMID: 29080699.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Therapeutic potential of omega-3 fatty acid-derived epoxyeicosanoids in cardiovascular and inflammatory diseases. AU - Schunck,Wolf-Hagen, AU - Konkel,Anne, AU - Fischer,Robert, AU - Weylandt,Karsten-Henrich, Y1 - 2017/11/07/ PY - 2017/10/31/pubmed PY - 2018/12/12/medline PY - 2017/10/30/entrez KW - Bioactive lipid mediators KW - Cardiovascular disease KW - Cytochrome P450 enzymes KW - Omega-3 fatty acids SP - 177 EP - 204 JF - Pharmacology & therapeutics JO - Pharmacol. Ther. VL - 183 N2 - Numerous benefits have been attributed to dietary long-chain omega-3 polyunsaturated fatty acids (n-3 LC-PUFAs), including protection against cardiac arrhythmia, triglyceride-lowering, amelioration of inflammatory, and neurodegenerative disorders. This review covers recent findings indicating that a variety of these beneficial effects are mediated by "omega-3 epoxyeicosanoids", a class of novel n-3 LC-PUFA-derived lipid mediators, which are generated via the cytochrome P450 (CYP) epoxygenase pathway. CYP enzymes, previously identified as arachidonic acid (20:4n-6; AA) epoxygenases, accept eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3; DHA), the major fish oil n-3 LC-PUFAs, as efficient alternative substrates. In humans and rodents, dietary EPA/DHA supplementation causes a profound shift of the endogenous CYP-eicosanoid profile from AA- to EPA- and DHA-derived metabolites, increasing, in particular, the plasma and tissue levels of 17,18-epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP). Based on preclinical studies, these omega-3 epoxyeicosanoids display cardioprotective, vasodilatory, anti-inflammatory, and anti-allergic properties that contribute to the beneficial effects of n-3 LC-PUFAs in diverse disease conditions ranging from cardiac disease, bronchial disorders, and intraocular neovascularization, to allergic intestinal inflammation and inflammatory pain. Increasing evidence also suggests that background nutrition as well as genetic and disease state-related factors could limit the response to EPA/DHA-supplementation by reducing the formation and/or enhancing the degradation of omega-3 epoxyeicosanoids. Recently, metabolically robust synthetic analogs mimicking the biological activities of 17,18-EEQ have been developed. These drug candidates may overcome limitations of dietary EPA/DHA supplementation and provide novel options for the treatment of cardiovascular and inflammatory diseases. SN - 1879-016X UR - https://www.unboundmedicine.com/medline/citation/29080699/Therapeutic_potential_of_omega_3_fatty_acid_derived_epoxyeicosanoids_in_cardiovascular_and_inflammatory_diseases_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0163-7258(17)30266-8 DB - PRIME DP - Unbound Medicine ER -