The role of oxidized HDL in monocyte macrophage functions in the pathogenesis of atherosclerosis in Rhesus monkeys

The effect of oxidative modification of high-density lipoprotein (HDL) was assessed by incubation of normal HDL (obtained from Rhesus monkeys fed a st ock diet) with 5 mu M CuSO4 at 37 degrees C for 12 h/24 h. The physicochemi cal properties of oxidized-HDL (Ox-HDL) were found to be affected in terms of lipid peroxidation, as observed by the increased level of thiobarbituric acid reactive substances (nmol MDA/mg HDL protein). The biological propert ies of HDL were altered, since a decrease in the efflux of free cholesterol into the medium was found in the presence of Ox-HDL24h compared with norma l HDL (N-HDL). The binding, uptake and degradation of I-125-LDL by macropha ges increased in the presence of Ox-HDL24h. The activity of antioxidant enz ymes (superoxide dismutase, catalase and glutathione-peroxidase) was reduce d in monocytes in the presence of Ox-HDL. However, in the presence of N-HDL , the levels of antioxidant enzymes were maintained at a higher level than in the control (in the absence of HDL) monocytes. Furthermore, the number o f monocytes adhered to aortic endothelium were found to be increased in the presence of Ox-HDL. These findings suggest that HDL is susceptible to oxid ative modification. Since the parameters selected in the present study are involved in the pathogenesis of atherosclerosis, it can be postulated that the in vivo protection of HDL in atherosclerosis can be reversed in the cir cumstances in which HDL undergoes oxidative modification like low-density l ipoprotein (LDL).