The proposed studies address the general hypothesis that in preeclampsia, a hypertensive disease of pregnancy that is a leading cause of indicated premature delivery and fetal growth retardation, there is abnormal placenta production of lipid peroxides and vasoactive eicosanoids, and that these abnormalities contribute to the clinical symptoms of the disorder, such as hypertension, proteinuria and reduced uteroplacental blood flow. The proposed studies address mechanisms whereby placenta production of prostacyclin (PGl2), a hypotensive agent, is decreased and that of thromboxane (TX), a hypertensive agent, is increased in preeclampsia. Increased placental TX production in preeclampsia could be coupled to an increase in placenta secretion of lipid peroxides. Lipid peroxides can damage cell membranes, so elevated levels of lipid peroxides could be related to endothelial cell injury and decreased PG12 in preeclampsia. Placentas will be obtained from normally pregnant women and women with preeclampsia. Placental tissues will be incubated or perfused in vitro to study production rates, secretion rates and regulatory factors. Eicosanoids will be measured by specific radioimmunoassays and lipid peroxides by glutathione peroxidase/reductase oxidation of NADPH and malondialdehyde generation.
The specific aims are to determine: i) The compartmentalizatlon of TX and lipid peroxides in the human placenta and the control of their production rates by the trophoblast and cyclooxygenase enzyme in normal and preeclamptic pregnancies; 2) Whether compartmentalization of hydroxyeicosatetraenoic acid (HETE) production in the placenta can explain trophoblast inhibition of placental thromboxane; 3) Mechanisms for placenta vasoconstriction relating to an imbalance between TX and PG12 and increased levels of lipid peroxides.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD020973-08
Application #
2198129
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1985-02-10
Project End
1997-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
8
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
Vaughan, John E; Walsh, Scott W (2012) Activation of NF-?B in placentas of women with preeclampsia. Hypertens Pregnancy 31:243-51