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Oxygen radicals and atherosclerosis

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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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Authors and Affiliations

  1. Department of Pathology, University of Cambridge, USA

    K. L. H. Carpenter, C. E. Brabbs & M. J. Mitchinson

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  1. K. L. H. Carpenter
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  2. C. E. Brabbs
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  3. M. J. Mitchinson
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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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