title: Human cytochrome P450 epoxygenases: variability in expression and role in inflammation-related disorders.
abstract: Beyond their contribution to the metabolism of xenobiotics, cytochrome P450 (CYP) epoxygenases are actively involved in the metabolism of endogenous substances, like arachidonic acid (AA). The main human CYP epoxygenases, i.e. CYP2C8, CYP2C9, CYP2C19 and CYP2J2, convert AA to four regioisomer epoxyeicosatrienoic acids (EETs). EETs possess a wide range of established protective effects on the human cardiovascular system of which anti-inflammatory actions have gained great recent interest. The expression of CYP epoxygenases is regulated through an extremely complex network of nuclear receptors, microRNAs and genetic/epigenetic factors. Accordingly, a large number of biological variables as well as xenobiotics and environmental factors can influence the expression of CYP epoxygenases, resulting in a significant intra- and inter-individual variability in the expression and activity of these enzymes and subsequently in EET biosynthesis. Moreover, human CYP epoxygenases are mainly expressed in the liver; however, these enzymes are also expressed, at various extents, in most extrahepatic tissues, resulting in a marked inter-tissue variability in the expression of CYP epoxygenases. The inter-tissue, inter- and intra-individual variability in the expression of epoxygenases may lead to differences in the relative abundance of EETs among tissues, among individuals of a population and/or different ethnicities and in a given individual under various conditions. The variation in the abundance of EETs may explain, at least in part, the inter-tissue and inter-individual differences observed in the prevalence of inflammation-related disorders including cardiovascular disease, and why in a given individual, various conditions can contribute to the development of diseases with an important inflammatory component.
authors.affiliation: UMR INSERM U1122, IGE-PCV, Faculté de Pharmacie, Université de Lorraine, 30 Rue Lionnois, 54000 Nancy, France. Electronic address: pshahabi_md@yahoo.com.
authors.forename: Payman
authors.initials: P
authors.lastname: Shahabi
authors.affiliation: UMR INSERM U1122, IGE-PCV, Faculté de Pharmacie, Université de Lorraine, 30 Rue Lionnois, 54000 Nancy, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Siest
authors.affiliation: Division of Pharmacology and Neurobiology, Biozentrum of the University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Urs A
authors.initials: UA
authors.lastname: Meyer
authors.affiliation: UMR INSERM U1122, IGE-PCV, Faculté de Pharmacie, Université de Lorraine, 30 Rue Lionnois, 54000 Nancy, France; Department of Internal Medicine and Geriatrics, CHU Nancy-Brabois, Rue du Morvan, Vandœuvre-lès-Nancy 54500, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Visvikis-Siest
mesh_terms: D000367:Age Factors; D016718:Arachidonic Acid / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D004777:Environment; D044127:Epigenesis, Genetic; D015870:Gene Expression; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008099:Liver / Q000378:metabolism; D011110:Polymorphism, Genetic; D012737:Sex Factors; D015533:Transcriptional Activation
chemical_list: D015777:Eicosanoids; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases
keywords: Cytochrome P450; Epoxyeicosatrienoic acids; Epoxygenase; Inflammation; Variability