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The factor in EDHF: Cytochrome P450 derived lipid mediators and vascular signaling.
Vascul Pharmacol. 2016 11; 86:31-40.VP

Abstract

Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to generate epoxyeicosatrienoic acids (EETs). The latter are biologically active and reported to act as an endothelium-derived hyperpolarizing factor (EDHF) as well as to affect angiogenic and inflammatory signaling pathways. In addition to arachidonic acid, the CYP epoxygenases 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 to corresponding diols and epoxide hydrolase inhibition increases epoxide levels and demonstrates anti-hypertensive as well as anti-inflammatory effects. It seems that the overall consequences of CYP epoxygenase activation largely depend on enzyme substrate preference and the endogenous Ω-3/Ω-6 PUFA ratio. This review outlines the evidence for a physiological role for EETs in the regulation of vascular homeostasis.

Authors+Show Affiliations

Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany; DZHK (German Centre for Cardiovascular Research) partner site RhineMain, Germany. Electronic address: fleming@em.uni-frankfurt.de.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

26975734

Citation

Fleming, Ingrid. "The Factor in EDHF: Cytochrome P450 Derived Lipid Mediators and Vascular Signaling." Vascular Pharmacology, vol. 86, 2016, pp. 31-40.
Fleming I. The factor in EDHF: Cytochrome P450 derived lipid mediators and vascular signaling. Vascul Pharmacol. 2016;86:31-40.
Fleming, I. (2016). The factor in EDHF: Cytochrome P450 derived lipid mediators and vascular signaling. Vascular Pharmacology, 86, 31-40. https://doi.org/10.1016/j.vph.2016.03.001
Fleming I. The Factor in EDHF: Cytochrome P450 Derived Lipid Mediators and Vascular Signaling. Vascul Pharmacol. 2016;86:31-40. PubMed PMID: 26975734.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The factor in EDHF: Cytochrome P450 derived lipid mediators and vascular signaling. A1 - Fleming,Ingrid, Y1 - 2016/03/11/ PY - 2015/11/13/received PY - 2016/01/20/revised PY - 2016/03/06/accepted PY - 2016/3/16/pubmed PY - 2017/7/8/medline PY - 2016/3/16/entrez KW - Angiogenesis KW - Arachidonic acid KW - Epoxyeicosatrienoic acid KW - Hypertension KW - Soluble epoxide hydrolase SP - 31 EP - 40 JF - Vascular pharmacology JO - Vascul. Pharmacol. VL - 86 N2 - Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to generate epoxyeicosatrienoic acids (EETs). The latter are biologically active and reported to act as an endothelium-derived hyperpolarizing factor (EDHF) as well as to affect angiogenic and inflammatory signaling pathways. In addition to arachidonic acid, the CYP epoxygenases 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 to corresponding diols and epoxide hydrolase inhibition increases epoxide levels and demonstrates anti-hypertensive as well as anti-inflammatory effects. It seems that the overall consequences of CYP epoxygenase activation largely depend on enzyme substrate preference and the endogenous Ω-3/Ω-6 PUFA ratio. This review outlines the evidence for a physiological role for EETs in the regulation of vascular homeostasis. SN - 1879-3649 UR - https://www.unboundmedicine.com/medline/citation/26975734/The_factor_in_EDHF:_Cytochrome_P450_derived_lipid_mediators_and_vascular_signaling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1537-1891(15)30077-X DB - PRIME DP - Unbound Medicine ER -