title: Effects of lipoproteins from pre-eclamptic women on umbilical endothelial cell 6-oxo-prostaglandin f1alpha and endothelin 1 synthesis, and nitric oxide synthase 3 mRNA expression.
abstract: 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 F(1alpha) (6-oxo-PGF(1alpha); 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 microgram/ml) and lipoprotein-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(1alpha) and endothelin 1, and NOS3 mRNA expression, were measured at each time point. VLDL from pre-eclamptic women stimulated endothelial cell 6-oxo-PGF(1alpha) synthesis to a lesser extent than that from normal pregnant women (P<0.05). LDL from women with pre-eclampsia also stimulated 6-oxo-PGF(1alpha) 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(1alpha) 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-PGF(1alpha) 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-PGF(1alpha) synthesis observed in the pre-eclamptic syndrome.
authors.affiliation: University Department of Medicine, Royal Perth Hospital, Perth, 6847 Western Australia, Australia. abarden@cyllene.uwa.edu.au
authors.forename: A
authors.initials: A
authors.lastname: Barden
authors.forename: L J
authors.initials: LJ
authors.lastname: Beilin
authors.forename: K
authors.initials: K
authors.lastname: Both
authors.forename: J
authors.initials: J
authors.lastname: Ritchie
authors.forename: P
authors.initials: P
authors.lastname: Leedman
authors.forename: B N
authors.initials: BN
authors.lastname: Walters
authors.forename: C A
authors.initials: CA
authors.lastname: Michael
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000097:blood / Q000494:pharmacology*; D008079:Lipoproteins, VLDL / Q000097:blood / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D016133:Polymerase Chain Reaction; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D019332:Endothelin-1; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; D015121:6-Ketoprostaglandin F1 alpha; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III