Increased epoxyeicosatrienoic acids and reduced soluble epoxide hydrolase expression in the preeclamptic placenta. 2016

Francesco Dalle Vedove, and Cristiano Fava, and Houli Jiang, and Giovanni Zanconato, and John Quilley, and Matteo Brunelli, and Valeria Guglielmi, and Gaetano Vattemi, and Pietro Minuz
aDepartment of Medicine, Verona, Italy bDepartment of Pharmacology, New York Medical College, Valhalla, New York, USA cDepartment of Surgical Sciences, Dentistry, Gynecology and Pediatrics dDepartment of Diagnostics and Public Health eDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy *These authors contributed equally to the study.

Epoxyeicosatrienoic acids (EETs) derived from cytochrome P450 (CYP)-dependent metabolism of arachidonic acid are increased in the plasma of women with preeclampsia as compared with normal pregnancy and are significantly higher in fetal than in maternal plasma and erythrocytes. We hypothesized that differences in EET synthesis or metabolism in the feto-placental unit contributed to the observed differences in circulating EETs. To evaluate EETs, formation as well as the expression of relevant CYP isoforms and the metabolizing enzyme, soluble epoxide hydrolase (sEH), biopsies of placenta were collected from 19 normal pregnancy and 10 preeclampsia at the time of cesarean section delivery. EETs were extracted from tissue homogenates and analyzed by liquid chromatography coupled with tandem mass spectrometry. Both cis-EETs and trans-EETs were detected in the placenta. Concentration of total EETs was higher in the placenta from preeclampsia compared with normal pregnancy (2.37 ± 1.42 ng/mg vs. 1.20 ± 0.72 ng/mg, mean ± SD, P < 0.01), especially the 5,6-, 8,9- and 11,12-EETs, measured in a subgroup of tissue samples (normal pregnancy = 10, preeclampsia = 5). By immunohistochemistry, sEH, CYP2J2, CYP4A11 were present in placental villi with different pattern distribution, whereas CYP2C8 was not detectable. Neither were CYP2J2, CYP4A11, and CYP2C8 detected in the umbilical cord. Western blot analysis of placenta homogenates showed reduced expression of sEH in preeclampsia as compared with normal pregnancy. Increased EETs in the placenta and umbilical cord are associated with the presence of CYP2J2, whereas reduced expression of sEH in preeclampsia may be the key factor of increased EETs in the placenta.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D010920 Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (CHORIONIC VILLI) derived from TROPHOBLASTS and a maternal portion (DECIDUA) derived from the uterine ENDOMETRIUM. The placenta produces an array of steroid, protein and peptide hormones (PLACENTAL HORMONES). Placentoma, Normal,Placentome,Placentas,Placentomes
D011225 Pre-Eclampsia A complication of PREGNANCY, characterized by a complex of symptoms including maternal HYPERTENSION and PROTEINURIA with or without pathological EDEMA. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease. Toxemias, Pregnancy,EPH Complex,EPH Gestosis,EPH Toxemias,Edema-Proteinuria-Hypertension Gestosis,Gestosis, EPH,Hypertension-Edema-Proteinuria Gestosis,Preeclampsia,Preeclampsia Eclampsia 1,Pregnancy Toxemias,Proteinuria-Edema-Hypertension Gestosis,Toxemia Of Pregnancy,1, Preeclampsia Eclampsia,1s, Preeclampsia Eclampsia,EPH Toxemia,Eclampsia 1, Preeclampsia,Eclampsia 1s, Preeclampsia,Edema Proteinuria Hypertension Gestosis,Gestosis, Edema-Proteinuria-Hypertension,Gestosis, Hypertension-Edema-Proteinuria,Gestosis, Proteinuria-Edema-Hypertension,Hypertension Edema Proteinuria Gestosis,Of Pregnancies, Toxemia,Of Pregnancy, Toxemia,Pre Eclampsia,Preeclampsia Eclampsia 1s,Pregnancies, Toxemia Of,Pregnancy Toxemia,Pregnancy, Toxemia Of,Proteinuria Edema Hypertension Gestosis,Toxemia Of Pregnancies,Toxemia, EPH,Toxemia, Pregnancy,Toxemias, EPH
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D003577 Cytochrome P-450 Enzyme System A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism. Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D004851 Epoxide Hydrolases Enzymes that catalyze reversibly the formation of an epoxide or arene oxide from a glycol or aromatic diol, respectively. Epoxide Hydrase,Epoxide Hydrases,Epoxide Hydratase,Epoxide Hydratases,Epoxide Hydrolase,9,10-Epoxypalmitic Acid Hydrase,Microsomal Epoxide Hydrolase,Styrene Epoxide Hydrolase,9,10 Epoxypalmitic Acid Hydrase,Acid Hydrase, 9,10-Epoxypalmitic,Epoxide Hydrolase, Microsomal,Epoxide Hydrolase, Styrene,Hydrase, 9,10-Epoxypalmitic Acid,Hydrase, Epoxide,Hydrases, Epoxide,Hydratase, Epoxide,Hydratases, Epoxide,Hydrolase, Epoxide,Hydrolase, Microsomal Epoxide,Hydrolase, Styrene Epoxide,Hydrolases, Epoxide
D004852 Epoxy Compounds Organic compounds that include a cyclic ether with three ring atoms in their structure. They are commonly used as precursors for POLYMERS such as EPOXY RESINS. Epoxide,Epoxides,Epoxy Compound,Oxiranes,Compound, Epoxy,Compounds, Epoxy
D004912 Erythrocytes Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN. Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D005260 Female Females
D005333 Fetus The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN. Fetal Structures,Fetal Tissue,Fetuses,Mummified Fetus,Retained Fetus,Fetal Structure,Fetal Tissues,Fetus, Mummified,Fetus, Retained,Structure, Fetal,Structures, Fetal,Tissue, Fetal,Tissues, Fetal

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