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.