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. 2016 Jul;34(7):1364-70.
doi: 10.1097/HJH.0000000000000942.

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

Francesco Dalle Vedove  1 , Cristiano Fava, Houli Jiang, Giovanni Zanconato, John Quilley, Matteo Brunelli, Valeria Guglielmi, Gaetano Vattemi, Pietro Minuz
Affiliations

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

Francesco Dalle Vedove et al. J Hypertens. 2016 Jul.

Abstract

Background: 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.

Method: 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.

Results: 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.

Conclusion: 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.

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Conflict of interest statement

Conflicts of interest

There are no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Total epoxyeicosatrienoic acids concentration in the placenta of normotensive and preeclamptic pregnant women. Data are expressed as ng/mg of dry tissue. Bar indicates mean. P < 0.05 also by nonparametric test.
FIGURE 2
FIGURE 2
Immunohistochemistry of soluble epoxide hydrolase in the umbilical cord and placenta. Tissue sections of the umbilical cord showing the Warthon’s jelly and one vascular structure at 10× magnification under optical microscope and a tissue section showing intermixed villi from placenta. Soluble epoxide hydrolase immunoexpression was observed in mesenchymal elements of the umbilical cord (arrows M, 20× magnification), and evidenced as weak signal in 1–3 cells per each villous (arrows V, 10× magnification), with an homogeneous pattern of distribution in the placenta (20×).
FIGURE 3
FIGURE 3
Immunohistochemistry of cytochrome P450 isoform 2J2 in the placenta of a normotensive woman. Tissue section from placenta showing variable sizes of villi. Morphological details regarding the cytotrophoblast and syncytiotrophoblast (arrows). cytochrome P450 isoform 2J2 was detectable in the mesenchymal elements (arrows M) of placenta (scattered in 10–40%, up to 50% of villi), but not in the umbilical cord (data not shown).
FIGURE 4
FIGURE 4
Western blot and quantitative analysis of soluble epoxide hydrolase protein expression. Soluble epoxide hydrolase was detected as a band corresponding to a molecular weight of ~60 kDa (a). A few non specific bands were present mainly at low molecular weight. Box plot represents the results of the
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References

    1. Young BC, Levine RJ, Karumanchi S. Pathogenesis of preeclampsia. Annu Rev Pathol. 2010;5:173–192. - PubMed
    1. Herse F, Lamarca B, Hubel CA, Kaartokallio T, Lokki AI, Ekholm E, et al. Cytochrome P450 subfamily 2J polypeptide 2 expression and circulating epoxyeicosatrienoic metabolites in preeclampsia. Circulation. 2012;126:2990–2999. - PMC - PubMed
    1. Spector AA, Fang X, Snyder GD, Weintraub NL. Epoxyeicosatrienoic acids (EETs): metabolism and biochemical function. Prog Lipid Res. 2004;43:55–90. - PubMed
    1. El-Sherbeni AA, El-Kadi AOS. The role of epoxide hydrolases in health and disease. Arch Toxicol. 2014;88:2013–2032. - PubMed
    1. Luksha L, Nisell H, Luksha N, Kublickas M, Hultenby K, Kublickiene K. Endothelium-derived hyperpolarizing factor in preeclampsia: heterogeneous contribution, mechanisms, and morphological prerequisites. Am J Physiol Regul Integr Comp Physiol. 2008;294:R510–R519. - PubMed

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