Measurement of vasoactive metabolites (hydroxyeicosatetraenoic and epoxyeicosatrienoic acids) in uterine tissues of normal and compromised human pregnancy.
BACKGROUND
Preeclampsia and intrauterine growth restriction define two disorders of a multifactorial etiology that compromise maternal and fetal well being as well as cardiovascular health in later life. Many of the overt symptoms of preeclampsia are attributable to the systemic endothelial dysfunction observed in the uteroplacental and systemic circulation, leading to a generalized vasoconstriction, hypertension and inadequate placental perfusion. Mounting evidence implicates nonprostanoid eicosanoids, epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs) in the control of vascular function and dysfunction.


OBJECTIVE
To determine whether levels of EETs and HETEs are altered in preeclampsia and intrauterine growth restriction compared with normal term pregnancy.


METHODS
An analytical liquid chromatography-tandem mass spectrometry profiling method was utilized in order to analyze differential levels of EETs and HETEs in intrauterine tissues of term nonlaboring, laboring and preeclamptic women as well as women with a growth-restricted pregnancy.


RESULTS
Placentae of preeclamptic women contained significantly (P < 0.05) larger amounts of 5-HETE, 12-HETE and 15-HETE known to possess either vasoconstrictive or proinflammatory actions. Laboring tissues were characterized by significantly higher (P < 0.05) EET levels in the amnion compared with the other clinical groups. EET and HETE levels in preeclampsia and intrauterine growth restriction were positively correlated (P < 0.05), whereas in normal and laboring pregnancies, EETs and HETEs were negatively correlated.


CONCLUSIONS
Increased production of 5-HETE, 12-HETE and 15-HETE metabolites in preeclamptic placentae indicates an important role for this family of eicosanoids in the cause of this disease.
Pearson
Timothy
T
Academic Division of Obstetrics & Gynaecology, University of Nottingham, The Medical School, The Royal Derby Hospital, Derby, UK.
Zhang
JiHong
J
Arya
Pratibha
P
Warren
Averil Y
AY
Ortori
Catherine
C
Fakis
Apostolos
A
Khan
Raheela N
RN
Barrett
David A
DA
D002853:Chromatography, Liquid; D004852:Epoxy Compounds / Q000378:metabolism*; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D011247:Pregnancy; D053719:Tandem Mass Spectrometry; D014599:Uterus / Q000378:metabolism*
D004852:Epoxy Compounds; D006893:Hydroxyeicosatetraenoic Acids