title: Effects of free fatty acids found increased in women who develop pre-eclampsia on the ability of endothelial cells to produce prostacyclin, cGMP and inhibit platelet aggregation.
abstract: Recently, we showed that levels of circulating free fatty acids are increased in women who later develop pre-eclampsia long before the clinical onset of the disease. Among the serum free fatty acids, oleic-, linoleic-, and palmitic acid were found to be increased by 37, 25 and 25%, respectively. In the present study we asked if these free fatty acids can interfere with endothelial cell functions. Cultured endothelial cells were exposed to linoleic-, oleic- and palmitic acid in concentrations ranging from 0.016 to 0.133 mumol ml-1, resulting in molar ratios of free fatty acids to albumin of 0.2-1.6. We found that among these fatty acids, linoleic acid reduced the thrombin-stimulated prostacyclin release by 30-60%, oleic acid by 10-30%, whereas palmitic acid had no effect. Endothelial cells incubated in presence of linoleic acid showed a concentration-dependent reduction in prostacyclin release in response to thrombin, and cells incubated with linoleic acid for up to 28 h, showed a reduced thrombin-induced prostacyclin release at every time point. Endothelial level of cGMP mainly reflected the synthesis of endothelium-derived relaxing factor/nitrogen monoxide (EDRF/NO), since blocking of the endogenous production of EDRF/NO with N-omega-nitro-L-arginine, resulted in about 90% reduction in cGMP-content of the endothelial cells. Incubation with linoleic acid reduced the endothelial cGMP level by 70%. Linoleic acid reduced the endothelial cells ability to inhibit platelet aggregation by 10-45%, (p = 0.0019). It was concluded that linoleic acid impedes the ability of the endothelial cells to produce prostacyclin and cGMP, and to inhibit platelet aggregation.
authors.affiliation: Department of Obstetrics and Gynecology, Aker University Hospital, Oslo, Norway.
authors.forename: M J
authors.initials: MJ
authors.lastname: Endresen
authors.forename: E
authors.initials: E
authors.lastname: Tøsti
authors.forename: H
authors.initials: H
authors.lastname: Heimli
authors.forename: B
authors.initials: B
authors.lastname: Lorentzen
authors.forename: T
authors.initials: T
authors.lastname: Henriksen
mesh_terms: D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000502:physiology*; D005260:Female; D006801:Humans; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy
chemical_list: D005230:Fatty Acids, Nonesterified; D008041:Linoleic Acids; D009829:Oleic Acids; D010169:Palmitic Acids; D019301:Oleic Acid; D019308:Palmitic Acid; D009569:Nitric Oxide; D019787:Linoleic Acid; D011464:Epoprostenol; D006152:Cyclic GMP