THE EXPRESSION AND ACTIVITY OF PROSTAGLANDIN-H SYNTHASE-2 IS ENHANCEDIN TROPHOBLAST FROM WOMEN WITH PREECLAMPSIA

Preeclampsia is associated with altered biosynthesis of vasoactive pro stanoids in placental villi. The two isozymes of prostaglandin H synth ase (PGHS) are essential for prostanoid synthesis. We tested the hypot hesis that PGHS-2 expression is elevated in trophoblast from preeclamp tic women, compared with trophoblast from healthy women. Using immunof luorescent staining, we demonstrated a higher PGHS-2 expression in vil li 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 o f both thromboxane and prostaglandin E-2, two products of PGHS activit y. The increased prostanoid production by trophoblast from preeclampti c 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 fro m normal pregnancies. The increased production of prostanoids may cont ribute to the clinical syndrome of preeclampsia. Our data suggest that a selective inhibitor of PGHS-2 might provide a therapeutic alternati ve to prophylactic low-dose aspirin in modifying the prostanoid profil e in preeclampsia.