title: CYP-eicosanoids--a new link between omega-3 fatty acids and cardiac disease?
abstract: Fish oil omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) protect against arrhythmia and sudden cardiac death by largely unknown mechanisms. Recent in vitro and in vivo studies demonstrate that arachidonic acid (AA) metabolizing cytochrome P450-(CYP) enzymes accept EPA and DHA as efficient alternative substrates. Dietary EPA/DHA supplementation causes a profound shift of the cardiac CYP-eicosanoid profile from AA- to EPA- and DHA-derived epoxy- and hydroxy-metabolites. CYP2J2 and other CYP epoxygenases preferentially epoxidize the ω-3 double bond of EPA and DHA. The corresponding metabolites, 17,18-epoxy-EPA and 19,20-epoxy-DHA, dominate the CYP-eicosanoid profile of the rat heart after EPA/DHA supplementation. The (ω-3)-epoxyeicosanoids show highly potent antiarrhythmic properties in neonatal cardiomyocytes, suggesting that these metabolites may specifically contribute to the cardioprotective effects of omega-3 fatty acids. This hypothesis is discussed in the context of recent findings that revealed CYP-eicosanoid mediated mechanisms in cardiac ischemia-reperfusion injury and maladaptive cardiac hypertrophy.
authors.affiliation: Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Westphal
authors.forename: Anne
authors.initials: A
authors.lastname: Konkel
authors.forename: Wolf-Hagen
authors.initials: WH
authors.lastname: Schunck
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000889:Anti-Arrhythmia Agents / Q000378:metabolism / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D001145:Arrhythmias, Cardiac / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D006332:Cardiomegaly / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000378:metabolism / Q000494:pharmacology; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D016757:Death, Sudden, Cardiac / Q000517:prevention & control*; D004281:Docosahexaenoic Acids / Q000378:metabolism* / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000378:metabolism* / Q000494:pharmacology; D005395:Fish Oils / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D015427:Reperfusion Injury
chemical_list: D000889:Anti-Arrhythmia Agents; C000717350:CYP2J2 protein, human; D002316:Cardiotonic Agents; D005395:Fish Oils; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D015118:Eicosapentaenoic Acid; D000090762:Cytochrome P-450 CYP2J2