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 in creased in women who later develop pre-eclampsia long before the clini cal onset of the disease. Among the serum free fatty acids, oleic-, li noleic-, and palmitic acid were found to be increased by 37, 25 and 25 %, respectively. In the present study we asked if these free fatty aci ds can interfere with endothelial cell functions. Cultured endothelial cells were exposed to linoleic-, oleic- and palmitic acid in concentr ations ranging from 0.016 to 0.133 mu mol ml(-1), resulting in molar r atios of free fatty acids to albumin of 0.2-1.6. We found that among t hese fatty acids, linoleic acid reduced the thrombin-stimulated prosta cyclin release by 30-60%, oleic acid by 10-30%, whereas palmitic acid had no effect. Endothelial cells incubated in presence of linoleic aci d showed a concentration-dependent reduction in prostacyclin release i n response to thrombin, and cells incubated with linoleic acid for up to 28 h, showed a reduced thrombin-induced prostacyclin release at eve ry time point. Endothelial level of cGMP mainly reflected the synthesi s of endothelium-derived relaxing factor/nitrogen monoxide (EDRF/NO), since blocking of the endogenous production of EDRF/NO with N-omega-ni tro-L-arginine, resulted in about 90% reduction in cGMP-content of the endothelial cells. Incubation with linoleic acid reduced the endothel ial cGMP level by 70%. Linoleic acid reduced the endothelial cells abi lity to inhibit platelet aggregation by 10-45%, (p = 0.0019). It was c oncluded that linoleic acid impedes the ability of the endothelial cel ls to produce prostacyclin and cGMP, and to inhibit platelet aggregati on.