Journal
JOURNAL OF CARDIOLOGY
Volume 54, Issue 3, Pages 368-374Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jjcc.2009.06.004
Keywords
Eicosapentaenoic acid; Cytochrome P-450; Peroxisome proliferator-activated receptor gamma; Endothelial cells
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omega-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 endothetial 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) gamma 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 PPAR gamma in endothelial cells and indicate a novel protective role of EPA and PPAR gamma against vascular inflammation. (C) 2009 Japanese College of Cardiology. Published by Elsevier Ireland Ltd. All rights reserved.
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