Summary
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.
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Abbreviations
- AX/ORO:
-
alcohol-xylene/Oil red O
- BHA:
-
butylated hydroxyanisole
- BHT:
-
butylated hydroxytoluene
- BSA:
-
bovine serum albumin
- C/BSA:
-
cholesterol-bovine serum albumin artifical lipoprotein
- CA/BSA:
-
cholesteryl arachidonate-bovine serum albumin artifical lipoprotein
- CD:
-
cholest-5-en-3β,7β-diol
- CL:
-
cholesteryl linoleate
- CL/BSA:
-
cholesteryl linoleate-bovine serum albumin artifical lipoprotein
- CO:
-
cholesteryl oleate
- CO/BSA:
-
cholesteryl oleate-bovine serum albumin artifical lipoprotein
- DMEM:
-
Dulbecco's modification of Eagle's medium
- EDTA:
-
ethylenediamine-tetraacetic acid
- FACS:
-
Fluorescence-activated cell sorter
- GC:
-
gas chromatography
- GC-MS:
-
gas chromatographymass spectrometry
- HMGCoA:
-
3-hydroxy-3-methyl-glutaryl-coenzyme A
- HMM:
-
human monocyte-macrophages
- HETEs:
-
hydroxyeicosatetraenoic acids
- HODEs:
-
hydroxyoc-tadecadienoic acids
- LDL:
-
low density lipoprotein
- LPD-FCS:
-
lipoprotein-deficient foetal calf serum
- LPD-HS:
-
lipoprotein-deficient human AB serum
- mRNA:
-
messenger ribonucleic acid
- MPM:
-
mouse peritoneal macrophages
- ORO:
-
oil red O
- USP:
-
United States Pharmacopeia
- WHHL:
-
Watanabe heritable hyperlipidemic
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Manuscripts published in this issue were the matter of a Symposium held at the University of Ulm, April 24–27, 1991
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Carpenter, K.L.H., Brabbs, C.E. & Mitchinson, M.J. Oxygen radicals and atherosclerosis. Klin Wochenschr 69, 1039–1045 (1991). https://doi.org/10.1007/BF01645155
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DOI: https://doi.org/10.1007/BF01645155