The expression and activity of prostaglandin H synthase-2 is enhanced in trophoblast from women with preeclampsia.
Preeclampsia is associated with altered biosynthesis of vasoactive prostanoids in placental villi. The two isozymes of prostaglandin H synthase (PGHS) are essential for prostanoid synthesis. We tested the hypothesis that PGHS-2 expression is elevated in trophoblast from preeclamptic women, compared with trophoblast from healthy women. Using immunofluorescent staining, we demonstrated a higher PGHS-2 expression in villi from preeclampsia, compared with normal pregnancy. Cytotrophoblasts cultured from placentas of preeclamptic women expressed higher levels of PGHS-2 compared with cytotrophoblasts from normal placentas. This enhanced expression of PGHS-2 correlated with increased media levels of both thromboxane and prostaglandin E2, two products of PGHS activity. The increased prostanoid production by trophoblast from preeclamptic women was markedly reduced by NS-398, a specific inhibitor of PGHS-2. We conclude that both expression and activity of PGHS-2 are enhanced in trophoblasts from preeclamptic women compared with trophoblast from normal pregnancies. The increased production of prostanoids may contribute to the clinical syndrome of preeclampsia. Our data suggest that a selective inhibitor of PGHS-2 might provide a therapeutic alternative to prophylactic low-dose aspirin in modifying the prostanoid profile in preeclampsia.
Johnson
R D
RD
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Sadovsky
Y
Y
Graham
C
C
Anteby
E Y
EY
Polakoski
K L
KL
Huang
X
X
Nelson
D M
DM
D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009578:Nitrobenzenes / Q000494:pharmacology; D010920:Placenta / Q000166:cytology / Q000201:enzymology; D011225:Pre-Eclampsia / Q000201:enzymology*; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000009:adverse effects / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D013449:Sulfonamides / Q000494:pharmacology; D014327:Trophoblasts / Q000201:enzymology*
D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009578:Nitrobenzenes; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D011451:Prostaglandin-Endoperoxide Synthases