Effects of lipoproteins from pre-eclamptic women on umbilical endothelial cell 6-oxo-prostaglandin F-I alpha and endothelin I synthesis, and nitric oxide synthase 3 mRNA expression

In order to evaluate whether lipid abnormalities may contribute to endothel ial dysfunction in pre-eclampsia, the present study examined the in vitro e ffects of very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL ) and high-density lipoprotein (HDL), isolated from women with pre-eclampsi a and matched controls, on the endothelial synthesis of 6-oxoprostaglandin F-1 alpha (6-oxo-PGF(1 alpha); a metabolite of prostacyclin) and endothelin I, and on the expression of nitric oxide synthase 3 (NOS3) mRNA. VLDL, LDL and HDL cholesterol were isolated from 20 pre-eclamptic and 20 age- and ge station-matched normal pregnant women. The lipoproteins (50 mu g/ml) and li poprotein-free control plasma were incubated for 1, 3 and 6 h at 37 degrees C with a human umbilical endothelial cell line. The synthesis of 6-oxo-PGF (1 alpha) and endothelin I, and NOS3 mRNA expression, were measured at each time point. VLDL from pre-eclamptic women stimulated endothelial cell 6-ox o-PGF(1 alpha) synthesis to a lesser extent than that from normal pregnant women (P < 0.05). LDL from women with pre-eclampsia also stimulated 6-oxoPG F(1 alpha) synthesis to a lesser extent than LDL from normal pregnant women , but the effect was less sustained. The effect of HDL from women with pre- eclampsia on 6-oxo-PGF(1 alpha) synthesis was similar to that of HDL from n ormal pregnant women. The pre-incubation levels of lipid peroxides in VLDL and LDL were not different between the normal pregnant and pre-eclamptic wo men, and cannot account for the decrease in 6-oxo-PGF(1 alpha) synthesis. V LDL, LDL and HDL from women with pre-eclampsia did not affect endothelial c ell synthesis of endothelin I or expression of NOS3 mRNA differently from l ipoproteins from normal pregnant women. This study suggests that VLDL, and to a lesser extent. LDL, from women with pre-eclampsia could potentially co ntribute to the reduced systemic 6-oxo-PGF(1 alpha) synthesis observed in t he pre-eclamptic syndrome.