Eicosapentaenoic acid increases cytochrome P-450 2J2 gene expression and epoxyeicosatrienoic acid production via peroxisome proliferator-activated receptor γ in endothelial cells.
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.
Wang
Dahai
D
Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Hirase
Tetsuaki
T
Nitto
Takeaki
T
Soma
Masaaki
M
Node
Koichi
K
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D000813:Anilides / Q000494:pharmacology; D001095:Arachidonic Acids; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000502:physiology; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D042783:Endothelial Cells / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D013268:Stimulation, Chemical; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology
C410128:11,12-dihydroxyeicosatrienoic acid; C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D001095:Arachidonic Acids; D047495:PPAR gamma; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D003577:Cytochrome P-450 Enzyme System; D015118:Eicosapentaenoic Acid; D015126:8,11,14-Eicosatrienoic Acid