Plasma From Preeclamptic Women Stimulates Decidual Endothelial Cell Growth and Prostacyclin but Not Nitric Oxide Production: Close Correlation of Prostacyclin and Thromboxane Production
Restricted accessResearch articleFirst published online January, 2001
Plasma From Preeclamptic Women Stimulates Decidual Endothelial Cell Growth and Prostacyclin but Not Nitric Oxide Production: Close Correlation of Prostacyclin and Thromboxane Production
Objective:To examine the effect of plasma from preeclamptic women on production of the vasoactive substances prostacyclin, thromboxane, nitric oxide, and cyclic guanosine monophosphate (cGMP) by decidual endothelial cells; to determine any effects on cell growth and health; and to examine whether cells from preeclamptic women are activated compared with cells from normal women.
Methods:Decidual endothelial cells from normal and preeclamptic women were incubated for 24 hours in media containing 10% plasma from preeclamptic women or matched normal women. Prostacyclin and thromboxane production was measured, as was nitric oxide and cGMP production after a further 45-minute generation period in 2% test plasma. Cell numbers and lactate dehydrogenase release were also determined.
Results:In plasma from preeclamptic women, cells grew significantly faster (P < .05), prostacyclin production was increased (P < .05), and lactate dehydrogenase release was reduced (P < .01). Production of thromboxane, nitric oxide, and cGMP was not significantly affected. Decidual endothelial cells from preeclamptic women had increased growth (P < .0001) and produced more prostacyclin (P < .05) and nitric oxide (P < .001) than normal decidual endothelial cells. There were highly significant correlations between prostacyclin and thromboxane production for incubations in plasmas from preeclamptic women and between background levels of prostacyclin in each plasma from preeclamptic women and the prostacyclin produced in incubations containing that plasma (P < .0001).
Conclusion:We found that plasma from preeclamptic women contained a factor that stimulated endothelial cell growth and regulated production of related amounts of prostacyclin and thromboxane. The plasma level of this factor appeared to be related to background levels of prostacyclin. The results also indicated that decidual endothelial cells from preeclamptic women were in a relatively activated state.
1. Roberts JM. Endothelial dysfunction in preeclampsia. Semin Reprod Endocrinol1998;16:5-15.
2.
2. Roberts JM, Taylor RN, Goldfein A. Endothelial cell activation as a pathogenetic factor in preeclampsia. Semin Perinatol1991;15:86-93.
3.
3. Taylor RN, de Groot CJ, Cho YK, Lim KH. Circulating factors as markers and mediators of endothelial cell dysfunction in preeclampsia. Semin Reprod Endocrinol1998;16:17-31.
4.
4. Branch DW, Dudley DJ, LaMarche S, Mitchell MD. Sera from preeclamptic patients contain factor(s) that stimulate prostacyclin production by human endothelial cells. Prostagl Leukotrienes Essential Fatty Acids1992;45:191-195.
5.
5. Gallery EDM, Rowe J, Campbell S, Hawkins T. Effect of serum on secretion of prostacyclin and endothelin-1 by decidual endothelial cells from normal and pre-eclamptic pregnancies. Am J Obstet Gynecol1995;173:918-923.
6.
6. de Groot CJM, Davidge St, Friedman SA, McLaughlin MK, Roberts JM, Taylor RN. Plasma from preeclamptic women increases human endothelial cell prostacyclin production without changes in cellular enzyme activity or mass. Am J Obstet Gynecol1995;172:976-985.
7.
7. Davidge ST, Signorella AP, Hubel CA, Lykins DL, Roberts JM. Distinct factors in plasma of preeclamptic women increase endothelial nitric oxide or prostacyclin. Hypertension1996;28:758-764.
8.
8. Winn HN, Todd HM, Amon E, Al-Malt A, Molnar M, Hertelendy F. Effects of serum from preeclamptic women on prostacyclin production by human endothelial cells. J Maternal-Fetal Med1997;6:249-253.
9.
9. Wellings RP, Brockelsby JC, Baker P. Activation of endothelial cells by plasma from women with preeclampsia: differential effects on four endothelial cell types. J Soc Gynecol Investi1998;5:31-37.
10.
10. Musci TJ, Roberts JM, Rodgers MD, Taylor RN. Mitogenic activity is increased in the sera of preeclamptic women before delivery. Am J Obstet Gynecol1988;159:1446-1451.
11.
11. Taylor RN, Heilbron DC, Roberts JM. Growth factor activity in the blood of women in whom preeclampsia develops is elevated in early pregnancy. Am J Obstet Gynecol1990;163:1839-1844.
12.
12. ISSHP Working Party. Management of hypertension in pregnancy. Med J Aust1993;158:700-702.
13.
13. Gallery EDM, Rowe J, Jackson C, Schrieber L. Purification and culture of microvascular endothelium from late pregnancy decidual tissue. Am J Obstet Gynecol1991;165:191-196.
14.
14. Oliver MH, Harrison NK, Bishop JE, Cole PJ, Laurent GJ. A rapid and convenient assay for counting cells cultured in micro-well plates: Application for assessment of growth factors. J Cell Sci1989;92:513-518.
15.
15. Mitchell DB, Santone KS, Acosta D. Evaluation of cytotoxicity in cultured cells by enzyme leakage. J Tissue Cult Methods1981;6:113-116.
16.
16. Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnak JS, Tannenbaum SR. Analysis of nitrate, nitrite and 15N-nitrate in biological fluids. Anal Biochem1982;126:131-138.
17.
17. Lorentzen B, Henriksen T. Plasma lipids and vascular dysfunction in preeclampsia. Semin Reprod Endocrinol1998;16:33-39.
18.
18. Smarason AK, Allman KG, Young D, Redman CW. Elevated levels of serum nitrate, a stable end product of nitric oxide, in women with pre-eclampsia. Br J Obstet Gynaecol1997;104:538-543.
19.
19. Ranta V, Viinikka L, Halmesmaki E, Ylikorkala O. Nitric oxide production with preclampsia. Obstet Gynecol1999;93:442-445.
20.
20. Paarlberg KM, de Jong CL, van Geijn HP, van Kamp GJ, Heinen AG. Dekker GA. Vasoactive mediators in pregnancy-induced hypertensive disorders: A longitudinal study. Am J Obstet Gynecol1998;179:1559-1564.
21.
21. Friedman SA. Preeclampsia: A review of the role of prostaglandins. Obstet Gynecol1988;71:122-137.
23. Rowe J, Campbell S, Gallery EDM. Effects of hypoxia on regulation of prostanoid production in decidual endothelial cells in normal and preeclamptic pregnancy. J Soc Gynecol Investig2000;7:118-124.
24.
24. Brockelsby JC, Anthony FW, Johnson IR, Baker PN. The effects of vascular endothelial growth factor on endothelial cells: A potential role in preeclampsia. Am J Obstet Gynecol2000;182:176-183.
25.
25. Baker PN, Krasnow J, Roberts JM, Yeo KT. Elevated serum levels of vascular endothelial growth factor in patients with preeclampsia. Obstet Gynecol1995;86:815-821.
26.
26. Sharkey AM, Cooper JC, Balmforth JR, McLaren J, Clark DE, Charnock-Jones DS. Maternal plasma levels of vascular endothelial growth factor in normotensive pregnancies and in pregnancies complicated by preeclampsia. Eur J Clin Investig1996;26:1182-1185.
27.
27. Reuvenkamp A, Velsing-Aarts FV, Poulina IE, Capello JJ, Duits AJ. Selective deficit of angiogenic growth factors characterises pregnancies complicated by preeclampsia. Br J Obstet Gynaecol1999;106:1019-1022.
28.
28. Brockelsby J, Hayman R, Ahmed A, Warren A, Johnson I, Baker P. VEGF via vessel relaxation in pregnancy: Implications in the pathogenisis of preeclampsia. Labor Investig1999;79:1101-1111.
29.
29. Rodgers GM, Taylor RN, Roberts JM. Preeclampsia is associated with a serm factor cytotoxic to human endothelial cells. Am J Obstet Gynecol1988;159:908-914.
30.
30. Kupfeminc MJ, Mullen TA, Russell TL, Silver RK. Serum from patients with severe pre-eclampsia is not toxic to endothelial cells. J Soc Gynecol Investig1996;3:89-92.
31.
31. Endresen EJ, Tosti E, Lorentzen B, Henriksen T. Sera of preeclamptic women are not cytotoxic to endothelial cells in culture. Am J Obstet Gynecol1994;172:196-202.
32.
32. Mills JL, DerSimonian R, Raymond E, et al. Prostacyclin and thromboxane changes predating clinical onset of preeclampsia: A multicenter prospective study. JAMA1999;282:356-362.
33.
33. Smith AJ, Walters WA, Buckley NA. Gallagher L, Mason A, McPherson J. Hypertensive and normal pregnancy: A longitudinal study of blood pressure, distensibility of dorsal hand veins and the ratio of the stable metabolites of thromboxane A2 and prostacyclin in plasma. Br J Obstet Gynaecol1995;102:900-906.
