ENHANCEMENT OF PROSTACYCLIN PRODUCTION IN CULTURED BOVINE AORTIC ENDOTHELIAL-CELLS BY OXIDIZED GLYCATED LOW-DENSITY-LIPOPROTEIN

Oxidized low-density lipoprotein (oLDL) is implicated in the pathogenesis of atherosclerosis. The serum concentration of glycated LDL (gLDL) is increased in diabetics, and it is possible that oxidative modification of gLDL contributes to the increased incidence of atherosclerosis associated with diabetes. The mechanism and effect on prostacyclin (PGI(2)) production by cultured bovine aortic endothelial cells of oxidized glycated LDL (ogLDL) prepared in vitro have now been examined. Glycation of LDL was performed by incubating LDL with 20 mM glucose for 3 days, ogLDL was then prepared by incubation of gLDL with 1 mu M CuSO4 for 12 h. Both the electrophoretic mobility and the thiobarbituric acid reactive substance content of ogLDL were greater than those of native LDL (nLDL) or gLDL. Binding, cell-association, and degradation of ogLDL in endothelial cells were significantly greater than those of nLDL and gLDL. The stimulatory effect of ogLDL on PGI(2) production was significantly greater than that of nLDL or gLDL; this effect was dose dependent. Both cell-association and the stimulatory effect on PGI(2) production of oLDL were dependent on the extent of oxidation in a biphasic manner. Endothelial cells thus appear to protect against atherosclerosis by removing atherogenic lipoproteins and by producing PGI(2).