Effects of linoleic and oleic acid anilides on prostacyclin synthesis and fibrinolytic profile of human endothelial cells in culture: relevance to the toxic oil syndrome

Abstract

We evaluated the effects of fatty-acid anilides (FAA) on prostacyclin (PGI 2) synthesis and on the fibrinolytic properties of human umbilical vein endothelial cells. Preincubation of endothelial cells with oleic- and linoleic-anilides (OAA and LAA, respectively) resulted in a time- and concentration-dependent inhibition of ionophore A23187- and thrombin-induced PGI 2 synthesis. However, no significant effects of FAA on arachidonic acid-induced PGI 2 synthesis were found, except with 1000 μM LAA which inhibited cyclooxygenase activity after 24 h. In general terms, OAA showed similar inhibitory effects on PGI 2 production as did LAA, but with a shifted time course, since the production of PGI 2 at 24 h for OAA was similar to that observed for LAA at 2 h. The release of labeled arachidonic acid from cell membranes was significantly reduced (75–85%), after 24 h, with both FAA. The effect of 100 μM LAA on thrombin-induced PGI 2 production was rapid (within 15 min) and irreversible after 60 min. The recovery of PGI 2 synthesis after LAA treatment was blocked by cycloheximide, suggesting a decrease of phospholipase(s) activity or cessation of enzyme synthesis. Moreover, this reduced PGI 2 synthesis was not associated with [ 3H]adenine release. Our data indicate that FAA induce a significant impairment of stimulated PGI 2 synthesis and arachidonic acid release in endothelial cells, acting primarily as inhibitors of phospholipase(s) rather than of cyclooxygenase. Finally, both LAA and OAA induce an anti-fibrinolytic activity in these cells where major changes are observed in the plasminogen activator inhibitor and the urine-type plasminogen activator.