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 stock diet) with 5 microM CuSO4 at 37 degrees C for 12 h/24 h. The physicochemical 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 properties 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 normal HDL (N-HDL). The binding, uptake and degradation of 125I-LDL by macrophages increased in the presence of Ox-HDL24h. The activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione-peroxidase) was reduced 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 of monocytes adhered to aortic endothelium were found to be increased in the presence of Ox-HDL. These findings suggest that HDL is susceptible to oxidative 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 circumstances in which HDL undergoes oxidative modification like low-density lipoprotein (LDL).
Sharma
N
N
Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Desigan
B
B
Ghosh
S
S
Sanyal
S N
SN
Ganguly
N K
NK
Majumdar
S
S
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001011:Aorta / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology* / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D008076:Cholesterol, HDL / Q000097:blood; D003300:Copper / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007457:Iodine Radioisotopes; D015227:Lipid Peroxidation / Q000187:drug effects / Q000276:immunology; D008077:Lipoproteins, LDL / Q000097:blood*; D008253:Macaca mulatta; D008264:Macrophages / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction
D000975:Antioxidants; D008076:Cholesterol, HDL; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D003300:Copper