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Preeclampsia: the effects of serum on endothelial cell prostacyclin, endothelin, and cell membrane integrity
V C Zammit1, J A Whitworth, M A Brown
1Department of Renal Medicine, St. George Hospital, Sydney, Australia.
Insights
Serum from preeclamptic women stimulates less endothelin production but does not affect prostacyclin or cause endothelial cell damage in short-term incubation, contrary to initial hypotheses regarding hypertensive disorders of pregnancy.
Area of Science:
- Reproductive Medicine
- Vascular Biology
- Obstetrics
Background:
- Preeclampsia and gestational hypertension are hypertensive disorders of pregnancy.
- Endothelial cell dysfunction is implicated in these conditions.
- Prostacyclin and endothelin are key mediators of vascular tone and endothelial function.
Purpose of the Study:
- To investigate the effects of serum from women with preeclampsia or gestational hypertension on endothelial cells.
- To determine if serum alters prostacyclin production, endothelin levels, or causes endothelial cell damage.
Main Methods:
- Cultured endothelial cells were incubated with serum from nonpregnant, normal pregnant, preeclamptic, and gestational hypertensive women.
- Prostacyclin (6-keto-prostaglandin F1 alpha) and endothelin production were measured.
- Endothelial cell damage was assessed using a chromium release assay.
Main Results:
- Serum from normal pregnant women increased prostacyclin and decreased endothelin compared to nonpregnant women.
- No significant difference in prostacyclin production was observed between normal pregnant and hypertensive pregnant women.
- Serum from preeclamptic women induced less endothelin than serum from normal pregnant women; no cytotoxic effects were observed.
Conclusions:
- Serum from preeclamptic women stimulates less endothelin production than serum from normal pregnant women.
- Serum from preeclamptic women does not alter prostacyclin production or cause endothelial cell cytotoxicity after short-term incubation.
- These findings suggest a complex role for serum factors in endothelial cell responses during hypertensive disorders of pregnancy.
Objective:
Our purpose was to determine whether serum from women with preeclampsia or gestational hypertension (1) decreased endothelial cell prostacyclin, (2) increased endothelial cell endothelin, and (3) caused endothelial cell damage.
Study Design:
Production of 6-keto-prostaglandin F1 alpha and endothelin by cultured endothelial cells was measured after 48 hours' incubation with sera from 23 nonpregnant women, 23 normal pregnant women, 12 women with preeclampsia, and 11 women with gestational hypertension. Structure damage of endothelial cells was assessed by a chromium release assay.
Results:
Serum from normal pregnant women induced more endothelial prostacyclin but less endothelin than did serum form nonpregnant women (p<0.05). No difference was found between normal pregnant and hypertensive pregnant women for prostacyclin production, but serum of preeclamptic women induced less endothelin production than did that of normal pregnant women (p<0.05). Chromium 51 release by endothelial cells was similar between normal pregnant and hypertensive pregnant groups.
Conclusions:
Serum from preeclamptic women stimulates less endothelin production than does serum from normal pregnant women but does not alter prostacyclin production and is not cytotoxic to endothelial cells after short-term incubation.