Oxygen radicals and atherosclerosis.
There is increasing evidence that lipids, especially those in low density lipoprotein, may be oxidised during the development of atherosclerotic lesions. The lipid-laden "foam cells" of atherosclerosis are macrophages, which are known to produce oxygen radicals in their microbicidal role. The same process could result in oxidation of lipid or lipoprotein in atherosclerosis. In human atherosclerotic lesions, many of the macrophage foam cells also contain ceroid, an insoluble polymer formed by oxidation of mixtures of lipid and protein. Using in vitro systems, we have studied the possibility that macrophages may be responsible for the oxidation of lipid and/or lipoprotein. Experiments are described in which mouse peritoneal macrophages and human monocyte-derived macrophages have been shown to oxidise cholesteryl linoleate, added to the cultures in the form of an artificial lipoprotein, with the production of soluble oxidised lipids, including oxidised sterols, and, in the case of mouse peritoneal macrophages, abundant ceroid. The oxidation was inhibited by radical scavengers. Oxidised sterols are cytotoxic. It is thus conceivable that oxidised sterols produced by monocyte-macrophages may lead to necrosis and progression of the lesion. Possibilities for prevention of this oxidation are discussed.
Carpenter
K L
KL
Department of Pathology, University of Cambridge.
Brabbs
C E
CE
Mitchinson
M J
MJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001161:Arteriosclerosis / Q000503:physiopathology*; D002478:Cells, Cultured; D002566:Ceroid / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D005487:Foam Cells / Q000502:physiology*; D005609:Free Radicals; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000502:physiology; D010100:Oxygen / Q000502:physiology*
D000975:Antioxidants; D002566:Ceroid; D002788:Cholesterol Esters; D005609:Free Radicals; D008077:Lipoproteins, LDL; C021976:cholesteryl linoleate; D010100:Oxygen