title: Maternal and fetal epoxyeicosatrienoic acids in normotensive and preeclamptic pregnancies.
abstract: BACKGROUND
  Epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) are cytochrome P450 metabolites of arachidonic acid posited to act in the circulatory adaptation to pregnancy and the development of preeclampsia. Red blood cells (RBCs) may function as major contributors of cis- and trans-EETs.
  
  
  METHODS
  We performed paired analyses of EETs, dihydroxyeicosatrienoic acids (DHETs), and 20-HETE in RBCs, plasma, and urine from preeclamptic and normotensive pregnant and nonpregnant women. Blood from fetal and maternal circulation was collected. EETs, DHETs, and 20-HETE were analyzed by gas chromatography and liquid chromatography mass spectrometry. Vascular function and inflammation indices were analyzed.
  
  
  RESULTS
  Plasma EET is higher in normotensive (median, range; 9.9, 6.3-25.2ng/mL n = 29) and preeclamptic (10.9, 6.0-48.0ng/mL, n = 19) women than in nonpregnant controls (7.3, 3.7-10.2ng/mL, n = 19) and correlate with RBC EETs, C-reactive protein, and arterial stiffness. Renal production of EETs, measured as urinary DHETs, was reduced in preeclamptic (4.5, 1.6-24.5ng/mg creatinine) compared to normotensive (11.4, 1.6-44.5ng/mg creatinine) pregnancies. EETs are 3- to 5-fold greater in fetoplacental than in maternal circulation (RBCs 36.6, 13.1-69.4 vs. 12.5, 6.4-12.0ng/10(9) cells; plasma 31.6, 8.5-192.6 vs. 12.0, 6.8-48.0ng/mL). Both cis- and trans-EETs are present in fetal RBCs.
  
  
  CONCLUSIONS
  RBCs contribute to elevated levels of EETs in the fetoplacental circulation. EETs may modulate systemic and fetoplacental hemodynamics in normal and preeclamptic pregnancies. Decreased renal EET generation may be associated with the development of maternal renal dysfunction and hypertension in preeclampsia.
authors: Department of Pharmacology, New York Medical College, Valhalla, NY, USA.
authors: Houli
authors: H
authors: Jiang
authors: John C
authors: JC
authors: McGiff
authors: Cristiano
authors: C
authors: Fava
authors: Gabriella
authors: G
authors: Amen
authors: Elisa
authors: E
authors: Nesta
authors: Giovanni
authors: G
authors: Zanconato
authors: John
authors: J
authors: Quilley
authors: Pietro
authors: P
authors: Minuz
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D003430:Cross-Sectional Studies; D015777:Eicosanoids / Q000378:metabolism*; D004912:Erythrocytes / Q000502:physiology; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007231:Infant, Newborn / Q000378:metabolism*; D008875:Middle Aged; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy / Q000378:metabolism*; D011249:Pregnancy Complications, Cardiovascular / Q000378:metabolism* / Q000503:physiopathology; D011262:Pregnancy Trimester, Second / Q000378:metabolism; D011263:Pregnancy Trimester, Third / Q000378:metabolism; D059289:Vascular Stiffness / Q000502:physiology
chemical_list: D015777:Eicosanoids; D006893:Hydroxyeicosatetraenoic Acids; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D002097:C-Reactive Protein
references: Proc Natl Acad Sci U S A. 1990 Aug;87(15):5893-7
references: 2198572
references: J Cardiovasc Pharmacol Ther. 2010 Jun;15(2):112-9
references: 20200327
references: Br J Pharmacol. 2007 Aug;151(7):1033-40
references: 17558440
references: Prostaglandins Other Lipid Mediat. 2005 Jan;75(1-4):65-78
references: 15789616
references: J Biol Chem. 2004 Aug 27;279(35):36412-8
references: 15213230
references: J Cardiovasc Pharmacol. 2010 Oct;56(4):336-44
references: 20930591
references: J Hypertens. 2010 Dec;28(12):2429-37
references: 20852449
references: Am J Physiol Regul Integr Comp Physiol. 2012 Feb 1;302(3):R321-30
references: 22116511
references: Prostaglandins. 1989 Dec;38(6):615-24
references: 2517348
references: Adv Biosci Biotechnol. 2012 Jun 1;3(3):204-218
references: 24660109
references: J Lipid Res. 1965 Jul;6:428-31
references: 14336214
references: Am J Physiol Regul Integr Comp Physiol. 2002 Feb;282(2):R383-9
references: 11792647
references: Br J Pharmacol. 1998 Oct;125(3):455-60
references: 9806327
references: Am J Physiol Heart Circ Physiol. 2009 Aug;297(2):H759-64
references: 19465544
references: Biochem Biophys Res Commun. 1980 Oct 16;96(3):1261-6
references: 6159894
references: Exp Biol Med (Maywood). 2006 Dec;231(11):1744-52
references: 17138762
references: J Pharmacol Exp Ther. 2008 Jul;326(1):330-7
references: 18445784
references: Am J Obstet Gynecol. 1995 Oct;173(4):1058-64
references: 7485293
references: Am J Hypertens. 2009 Jun;22(6):687-92
references: 19282816
references: J Thromb Haemost. 2009 Mar;7(3):375-84
references: 19087223
references: Prostaglandins. 1997 Oct;54(4):677-87
references: 9440131
references: Pflugers Arch. 2010 May;459(6):881-95
references: 20224870
references: Antioxid Redox Signal. 2010 Feb;12(2):185-98
references: 19702440
references: Hypertension. 2008 May;51(5):1379-85
references: 18378855
references: Hypertension. 2004 Mar;43(3):623-8
references: 14757776
references: J Pharmacol Sci. 2008 Sep;108(1):79-88
references: 18776712
references: J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Dec 1;876(1):83-8
references: 19004672
references: Clin Sci (Lond). 2002 Oct;103(4):371-7
references: 12241535
references: Lancet. 2005 Feb 26-Mar 4;365(9461):785-99
references: 15733721