In order to evaluate whether lipid abnormalities may contribute to endothelial dysfunction in pre-eclampsia, the present study examined the in vitro effects of very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), isolated from women with pre-eclampsia and matched controls, on the endothelial synthesis of 6-oxo-prostaglandin F1α (6-oxo-PGF1α; a metabolite of prostacyclin) and endothelin 1, 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 gestation-matched normal pregnant women. The lipoproteins (50 μg/ml) and lipoprotein-free control plasma were incubated for 1, 3 and 6 h at 37 °C with a human umbilical endothelial cell line. The synthesis of 6-oxo-PGF1α and endothelin 1, and NOS3 mRNA expression, were measured at each time point. VLDL from pre-eclamptic women stimulated endothelial cell 6-oxo-PGF1α synthesis to a lesser extent than that from normal pregnant women (P< 0.05). LDL from women with pre-eclampsia also stimulated 6-oxo-PGF1α 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-PGF1α synthesis was similar to that of HDL from normal pregnant women. The pre-incubation levels of lipid peroxides in VLDL and LDL were not different between the normal pregnant and pre-eclamptic women, and cannot account for the decrease in 6-oxo-PGF1α synthesis. VLDL, LDL and HDL from women with pre-eclampsia did not affect endothelial cell synthesis of endothelin 1 or expression of NOS3 mRNA differently from lipoproteins from normal pregnant women. This study suggests that VLDL, and to a lesser extent LDL, from women with pre-eclampsia could potentially contribute to the reduced systemic 6-oxo-PGF1α synthesis observed in the pre-eclamptic syndrome.
Effects of lipoproteins from pre-eclamptic women on umbilical endothelial cell 6-oxo-prostaglandin F1α and endothelin 1 synthesis, and nitric oxide synthase 3 mRNA expression
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A. BARDEN, L. J. BEILIN, K. BOTH, J. RITCHIE, P. LEEDMAN, B. N. WALTERS, C. A. MICHAEL; Effects of lipoproteins from pre-eclamptic women on umbilical endothelial cell 6-oxo-prostaglandin F1α and endothelin 1 synthesis, and nitric oxide synthase 3 mRNA expression. Clin Sci (Lond) 1 December 1999; 97 (6): 697–706. doi: https://doi.org/10.1042/cs0970697
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