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

• Published in: Journal of cardiology Vol. 54; no. 3; pp. 368 - 374
• Main Authors: Wang, Dahai, MD, PhD, Hirase, Tetsuaki, MD, PhD, Nitto, Takeaki, PhD, Soma, Masaaki, PhD, Node, Koichi, MD, PhD, FJCC
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-12-2009
• Subjects: 8,11,14-Eicosatrienoic Acid - analogs & derivatives; 8,11,14-Eicosatrienoic Acid - metabolism; Anilides - pharmacology; Arachidonic Acids; Cardiovascular; Cells, Cultured; Cytochrome P-450; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - physiology; Docosahexaenoic Acids - pharmacology; Dose-Response Relationship, Drug; Eicosapentaenoic acid; Eicosapentaenoic Acid - pharmacology; Endothelial cells; Endothelial Cells - metabolism; Gene Expression - drug effects; Humans; Peroxisome proliferator-activated receptor γ; PPAR gamma - antagonists & inhibitors; PPAR gamma - physiology; RNA, Messenger - metabolism; Stimulation, Chemical; Time Factors; Umbilical Veins - cytology; Peroxisome proliferator-activated receptor γ; Eicosapentaenoic acid; Endothelial cells; Cytochrome P-450
• ISSN: 0914-5087; 1876-4738
• DOI: 10.1016/j.jjcc.2009.06.004

Summary 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.