CYP-eicosanoids--a new link between omega-3 fatty acids and cardiac disease?

Prostaglandins Other Lipid Mediat. 2011 Nov;96(1-4):99-108. doi: 10.1016/j.prostaglandins.2011.09.001. Epub 2011 Sep 16.

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.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Anti-Arrhythmia Agents / metabolism
  • Anti-Arrhythmia Agents / pharmacology
  • Arachidonic Acid / metabolism
  • Arrhythmias, Cardiac / metabolism*
  • Arrhythmias, Cardiac / physiopathology
  • Arrhythmias, Cardiac / prevention & control
  • Cardiomegaly / metabolism*
  • Cardiomegaly / physiopathology
  • Cardiomegaly / prevention & control
  • Cardiotonic Agents / metabolism
  • Cardiotonic Agents / pharmacology
  • Cytochrome P-450 Enzyme System / metabolism
  • Death, Sudden, Cardiac / prevention & control*
  • Docosahexaenoic Acids / metabolism*
  • Docosahexaenoic Acids / pharmacology
  • Eicosapentaenoic Acid / metabolism*
  • Eicosapentaenoic Acid / pharmacology
  • Fish Oils / metabolism*
  • Fish Oils / pharmacology
  • Humans
  • Mice
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / enzymology*
  • Rats
  • Reperfusion Injury

Substances

  • Anti-Arrhythmia Agents
  • Cardiotonic Agents
  • Fish Oils
  • Docosahexaenoic Acids
  • Arachidonic Acid
  • Cytochrome P-450 Enzyme System
  • Eicosapentaenoic Acid
  • arachidonate epoxygenase