Macrophages, lipid oxidation, ceroid accumulation and alpha-tocopherol depletion in human atherosclerotic lesions.
Necropsy samples of atherosclerotic lesions of different histological stages have been analysed. Ceroid was present in all the lesions, within lipid-laden macrophage foam cells and extracellularly in the atheromatous core of advanced lesions. Mean levels of 7 beta-hydroxycholesterol, 26-hydroxycholesterol and hydroxyoctadecadienoic acids were all significantly greater in lesions than in normal intima. Levels of hydroxycholesterols were very low or undetectable in normal intima. Fatty streaks showed the highest ratio of 7 beta-hydroxycholesterol to cholesterol, and the lowest ratio of linoleate to oleate, suggesting that this type of lesion experiences the greatest free radical activity. Levels of 26-hydroxycholesterol, a product of the cytochrome P-450 enzyme sterol 26-hydroxylase, and the ratio of 26-hydroxycholesterol to cholesterol were significantly higher in advanced lesions than in intermediate lesions or fatty streaks. The ratio of alpha-tocopherol to cholesterol levels varied widely in normal intima but was consistently low in lesions, especially those rich in macrophage foam cells, suggesting that oxidative activity in the lesion may lead to significant oxidation of the lesion constituents only after alpha-tocopherol has been depleted. Macrophage death was a characteristic feature of advanced lesions, with apoptotic bodies present, and occasionally, intact apoptotic cells were seen in lesions. These striking correlations between macrophages, lipid oxidation, alpha-tocopherol depletion, ceroid accumulation, and macrophage death in advanced lesions, strongly support a role for oxidative damage in atherosclerosis, and lend credence to the idea that alpha-tocopherol dietary supplementation may slow the progression of atherosclerosis in humans.
Carpenter
K L
KL
Department of Pathology, University of Cambridge, UK.
van der Veen
C
C
Taylor
S E
SE
Hardwick
S J
SJ
Clare
K
K
Hegyi
L
L
Mitchinson
M J
MJ
D001012:Aorta, Abdominal / Q000473:pathology; D001013:Aorta, Thoracic / Q000473:pathology; D001161:Arteriosclerosis / Q000201:enzymology / Q000473:pathology*; D002470:Cell Survival; D002566:Ceroid / Q000378:metabolism; D046508:Culture Techniques; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000032:analysis / Q000378:metabolism*; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000502:physiology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D014810:Vitamin E / Q000378:metabolism*
D002566:Ceroid; D006888:Hydroxycholesterols; D014810:Vitamin E