The Expression and Activity of Prostaglandin H Synthase-2 Is Enhanced in Trophoblast from Women with Preeclampsia1
Roger D. Johnson,
Yoel Sadovsky,
Carol Graham,
Eyal Y. Anteby,
Kenneth L. Polakoski,
Xiaohua Huang and
D. Michael Nelson
Department of Obstetrics and Gynecology, Washington University
School of Medicine, St. Louis, Missouri 63110
Address all correspondence and requests for reprints to: D. Michael Nelson, M.D., Ph.D., Department of Obstetrics and Gynecology, 4911 Barnes Hospital Plaza, St. Louis, Missouri 63110-1094. NELSON DM{at}kids.wustl.edu
Preeclampsia is associated with altered biosynthesis of vasoactive
prostanoidsin placental villi. The two isozymes of prostaglandin H
synthase(PGHS) are essential for prostanoid synthesis. We tested the
hypothesisthat PGHS-2 expression is elevated in trophoblast from
preeclampticwomen, compared with trophoblast from healthy women. Using
immunofluorescentstaining, we demonstrated a higher PGHS-2 expression
in villifrom preeclampsia, compared with normal pregnancy.
Cytotrophoblastscultured from placentas of preeclamptic women
expressed higherlevels of PGHS-2 compared with cytotrophoblasts from
normalplacentas. This enhanced expression of PGHS-2 correlated with
increasedmedia levels of both thromboxane and prostaglandin
E2, two productsof PGHS activity. The increased prostanoid
production by trophoblastfrom preeclamptic women was markedly reduced
by NS-398, a specificinhibitor of PGHS-2. We conclude that both
expression and activityof PGHS-2 are enhanced in trophoblasts from
preeclamptic womencompared with trophoblast from normal pregnancies.
The increasedproduction of prostanoids may contribute to the clinical
syndromeof preeclampsia. Our data suggest that a selective inhibitor
ofPGHS-2 might provide a therapeutic alternative to prophylactic
low-doseaspirin in modifying the prostanoid profile in preeclampsia.
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