OXIDIZED LDL AND REDUCTION OF THE ANTIAGGREGATING ACTIVITY OF NITRIC-OXIDE DERIVED FROM ENDOTHELIAL-CELLS

Oxidized LDL has been observed to induce abnormalities in endothelial function which may be relevant for the progression of atherosclerotic lesions. We studied in vitro the possible effects of oxidized LDL on t he antiaggregating activity of endothelial cells, which is dependent o n release of prostacyclin and nitric oxide. We used an experimental mo del in which cultured human endothelial cells were placed in the aggre gometer in contact with human platelets, after blockade of cyclo-oxyge nase by adding acetylsalicylic acid. In this way the antiaggregant eff ect of endothelial cells was dependent on the release of nitric oxide alone; prevention of antiaggregant activity by preincubation of endoth elial cells with 300 mu M L-N-G-mono-methyl arginine confirmed this. W hen this system was used, endothelial cells; (2-7.5 X 10(5)/ml) almost completely inhibited thrombin-induced (0.02-0.08 U/ml) platelet aggre gation (2 X 10(8) platelets/ml), measured according to Born (11.1% +/- 8.5 vs 68.6% +/- 12.6, M +/- SD). This antiaggregating activity was r educed when slightly oxidized LDL 100 mu g/ml (35.2% +/- 14.9, p <0.00 1), but not native LDL 100 mu g/ml (7.5% +/- 7.6), was added immediate ly before aggregation was induced. Incubation of endothelial cells wit h oxidized LDL 100 mu g/ml for 1 h did not affect the antiaggregating capacity, unless oxidized LDL was present during aggregation (18.3% +/ - 10.2 vs 35.8% +/- 9.6, p <0.02). No significant direct effect of eit her oxidized pr native LDL on stimulated platelet aggregation was obse rved. Our results indicate that slightly oxidized LDL can reduce the a ntiaggregating properties of the endothelium, probably by interaction with NO rather than through inhibition of its synthesis.