Objective:TO determine whether placenta and plasma of preeclamptic women contain factors that cause endothelial cell damage.
Methods:Placental extracts and plasma from preeclamptic and normotensive women were added to cultures of normal human umbilical vein endothelial cells and their effect on their viability, was determined by MTT reduction and 51chromium release.
Results:Placental exracts from normotensive and preeclamptic women were cytotoxic to endothelial cells, but not the plasma from both groups. Mean ± standard deviation values of cytotoxicity index in preeclamptic and normotensive placental extracts using the MTT reduction were 70.3 ± 6.76% and 51.4 ± 8.81%, respectively, showing a significant difference (P < .0001). Using the 51chromium-release assay, preeclamptic placental extracts showed cytotoxic effects of 87.6 ± 13.47% compared with 17 ± 20.60% in control patients. The cytotoxic activity decreased after trypsin digestion and heat treatment in both groups.
Conclusions:A cytotoxic factor to endothelial cells in placental extracts of preeclamptic women was identified. This compound is thermolabile and sensitive to trypsin digestion.
1. Fairlie FM, Sibai BM. Hypertensive diseases in pregnancy. In: Reece EA, Hobbins JC, Mahoney MJ, Petrie RH, eds. Medicine of the fetus and mother. Philadelphia: JB Lippincott, 1992:925-942.
2.
2. Deng L, Bremme K, Hansson L, Blombäck M. Plasma levels of von Willebrand factor and fibronectin as markers of presisting endocthelial damage in preeclampsia. Obstet Gynecol1994;84:941-945.
3.
3. McCartney C. The acute hypertensive disorders of pregnancy classified by renal histology. Gynecologia1969;167-214-220.
4.
4. Rodgers G, Taylor R, Roberts J. Preeclampsia is associated wtih a serum factor cytotoxic to human endothelial cells. Am J Obstet Gynecol1988;159:908-914.
5.
5. Tsukimori K, Maeda H, Shingu M, Koyanagi T, Nobunaga M, Nakano H. The possible role of endothelial cells in hypertensive disorders during pregnancy. Obstet Gynecol1992;80:229-233.
6.
6. Endresen M. Tøsti E, Lorentzen B, Henriksen, T. Sera of preeclamptic women are not cytotoxic to endothelial cells in culture. Am J Obstet Gynecol1995;172:196-201.
7.
7. Kupferminc M, Mullen T, Russell T, Silver R. Serum from patients with severe preeclampsia is not cytotoxic to endothelial cells. J Soc Gynecol Invest1996;3:89-92.
8.
8. Bustos-López H, Hong E, Vadillo-Ortega F, Castañeda G, Karchmer S. Potentiation of vascular responses using placental extracts from eclamptic women. Proc West Pharmacol Soc1991;34:189-193.
9.
9. Smárason A, Sargent Y, Starkey P, Redman C. The effect of placental synctiotrophoblast microvillous membranes from normal and pre-eclamptic women on the growth of endothelial cells in vitro. Br J Obstet Gynaecol1993;100:943-949.
10.
10. Smárason A, Sargent I, Redman C. Endothelial cell proliferation is suppressed by plasma but not serum from women with preeclampsia. Am J Obstet Gynecol1996;174:787-793.
11.
11. Vadillo F, Hong E, León H, et al. Vasoconstrictino induced by soluble factors derived from human placenta. Proc West Pharmacol Soc1991;34:183-187.
12.
12. Bradford M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of proteindye binding. Anal Biochem1976;72:248-254.
13.
13. Jaffe E, Nachman R, Becker C, Minick C. Culture of human endothelial cells derived from umbilical veins. J Clin Invest1973;52:2745-2756.
14.
14. Thornton S, Mueller S, Levine E. Human endothelial cells: Use of heparin in cloning and long-term serial cultivation. Science1983;222:623-625.
15.
15. Freshney RI. Culture of animal cells. A manual of basic technique. 2nd ed.New York: Wiley-Liss, 1987:257-288.
16.
16. Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods1983;65:55-63.
17.
17. Zawydiwski R, Duncan R. Spontaneous 51Cr release by isolated rat hepatocytes: AN indicator of membrane damage. In Vitro1978;14:707-714.
