title: Whatever happened to the epoxyeicosatrienoic Acid-like endothelium-derived hyperpolarizing factor? The identification of novel classes of lipid mediators and their role in vascular homeostasis.
abstract: CONCLUSIONS
  Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid (AA) to generate epoxyeicosatrienoic acids (EETs). The latter are biologically active and reported to act as an endothelium-derived hyperpolarizing factor as well as to affect angiogenic and inflammatory signaling pathways.
  
  
  BACKGROUND
  In addition to AA, the CYP enzymes also metabolize the ω-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid and docosahexaenoic acid to generate bioactive lipid epoxide mediators. The latter can be more potent than the EETs, but their actions are under investigated. The ω3-epoxides, like the EETs, are metabolized by the soluble epoxide hydrolase (sEH) to corresponding diols, and epoxide hydrolase inhibition increases epoxide levels and demonstrates anti-hypertensive as well as anti-inflammatory effects.
  
  
  RESULTS
  It seems that the overall consequences of CYP activation largely depend on enzyme substrate preference and the endogenous ω-3/ω-6 PUFA ratio.
  
  
  CONCLUSIONS
  More studies combining PUFA profiling with cell signaling and disease studies are required to determine the spectrum of molecular pathways affected by the different ω-6 and ω-3 PUFA epoxides and diols. Such information may help improve dietary studies aimed at promoting health via ω-3 PUFA supplementation and/or sEH inhibition.
authors.affiliation: Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University , Frankfurt am Main, Frankfurt, Germany .
authors.forename: Timo
authors.initials: T
authors.lastname: Frömel
authors.forename: Ingrid
authors.initials: I
authors.lastname: Fleming
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001685:Biological Factors / Q000737:chemistry / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000737:chemistry / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D015398:Signal Transduction
chemical_list: D001685:Biological Factors; D015525:Fatty Acids, Omega-3; C067410:endothelium-dependent hyperpolarization factor; D003577:Cytochrome P-450 Enzyme System; D015126:8,11,14-Eicosatrienoic Acid