CHRONIC EXPOSURE OF BOVINE AORTIC ENDOTHELIAL-CELLS TO NATIVE AND OXIDIZED LDL MODIFIES PHOSPHATIDYLINOSITOL METABOLISM

The aim of this study was to investigate the effects of chronic exposure to low density lipoprotein (LDL) and oxidised LDL (OXLDL) on phosphatidylinositol metabolism in bovine aortic endothelial cells. Basal levels of total inositol phosphates and inositol 1,4,5-trisphosphate were increased after both 18 and 66 h exposure to OXLDL 20 mu g/ml. Levels also tended to be increased after exposure to LDL but this only reached significance for LDL 20 mu g/ml after 18 h exposure. Absolute levels of inositol phosphates after stimulation with ATP were unaffected by incubation with LDL or OXLDL. However, when expressed as a percentage of basal levels, stimulated levels of inositol phosphates were reduced for ATP 10(-3) and 10(-4)M. Uptake of [H-3]inositol into the phosphatidylinositol cycle was reduced after incubation with LDL and OXLDL for either 18 or 66 h. The effect of OXLDL was greater than that of LDL. The antioxidants EDTA and N-acetylcysteine attenuated the effects of LDL but not OXLDL. In addition, catalase but not mannitol or superoxide dismutase modified the effect of LDL on [H-3]inositol uptake. These studies show that chronic exposure to OXLDL and to a lesser extent LDL can modify phosphatidylinositol metabolism in bovine aortic endothelial cells and that the effects of LDL may be attenuated by antioxidants and free radical scavengers. We hypothesise that the decreased uptake of [H-3]inositol could be related to an alteration in membrane structure and integrity and may reflect alteration in transport of a number of ions and molecules.