Eicosapentaenoic acid increases cytochrome P-450 2J2 gene expression and epoxyeicosatrienoic acid production via peroxisome proliferator-activated receptor γ in endothelial cells

Journal of cardiology
Dahai WangKoichi Node

Abstract

ω-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have beneficial effects on cardiovascular diseases. Cytochrome P-450 (CYP) 2J2 that is expressed in endothelial cells metabolizes arachidonic acids to biologically active epoxyeicosatrienoic acids (EETs) that possess anti-inflammatory and anti-thrombotic effects. We studied the effects of EPA and DHA on the expression of CYP 2J2 mRNA by reverse transcription-polymerase chain reaction in cultured human umbilical vein endothelial cells and found that EPA, but not DHA, increased the expression of CYP 2J2 mRNA in a dose-dependent and a time-dependent manner. EPA-induced CYP 2J2 expression was significantly inhibited by pretreatment with a peroxisome proliferator-activated receptor (PPAR) γ antagonist, GW9662. EPA, but not DHA, caused a significant increase in cellular levels of 11,12-dihydroxyeicosatrienoic acid that is a stable metabolite of 11,12-EET, which was blocked by pretreatment with GW9662. These data demonstrate that EPA increases CYP 2J2 mRNA expression and 11,12-EET production via PPARγ in endothelial cells and indicate a novel protective role of EPA and PPARγ against vascular inflammation.

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Citations

Oct 20, 2011·Cancer Metastasis Reviews·Ingrid Fleming
Dec 14, 2011·Circulation Journal : Official Journal of the Japanese Circulation Society·Takenori DomeiMasakiyo Nobuyoshi
Dec 4, 2012·Marine Drugs·Fraser D Russell, Corinna S Bürgin-Maunder
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Aug 6, 2016·PloS One·Haitham E El-SikhryJohn M Seubert
Nov 13, 2014·American Journal of Physiology. Endocrinology and Metabolism·Rui LiDao Wen Wang

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