EFFECTS OF FREE FATTY-ACIDS FOUND INCREASED IN WOMEN WHO DEVELOP PREECLAMPSIA ON THE ABILITY OF ENDOTHELIAL-CELLS TO PRODUCE PROSTACYCLIN, CGMP AND INHIBIT PLATELET-AGGREGATION

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 mu mol 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.