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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2078.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Vitamin E Supplementation of Human Macrophages Prevents Neither Foam Cell Formation Nor Increased Susceptibility of Foam Cells to Lysis by Oxidized LDL

Reto Asmis; Jennifer Jelk

From the Institute of Biochemistry, University of Basel, Basel, Switzerland

Correspondence to Dr Reto Asmis, Division of Cardiovascular Medicine, L543 KY Clinic, University of Kentucky, Lexington, KY 40536. E-mail rasmis{at}pop.uky.edu

Abstract—Several studies in macrophage cell lines, rodent macrophages, and animal models of atherosclerosis suggest that vitamin E may prevent the formation of foam cells. We tested this hypothesis in a recently developed, fully autologous in vitro model of human foam cell formation. During maturation, macrophages continuously increased their -tocopherol/total cholesterol ratio, demonstrating that these cells accumulate -tocopherol at an even higher rate than cholesterol. In the presence of unsupplemented serum, we observed no correlation between serum vitamin E levels and the increase in the cellular -tocopherol/total cholesterol ratio. In contrast, under supplemented conditions, a 3.1-fold increase in the mean serum -tocopherol/total cholesterol ratio resulted in a corresponding mean 3.5-fold increase in the cellular -tocopherol/total cholesterol ratio. Vitamin E loading had no effect on the lipid composition of macrophages and did not affect their growth. Foam cell formation was stimulated in mature unsupplemented and vitamin E–loaded macrophages for 1 week with 50 µg autologous aggregated low density lipoprotein (LDL) in the presence of unsupplemented and vitamin E–loaded serum, respectively. We observed no effect of vitamin E supplementation on the formation of foam cells. However, foam cell formation resulted in a 36% and 44% reduction in the cellular -tocopherol/total cholesterol ratio in unsupplemented and vitamin E–supplemented foam cells, respectively. The loss of vitamin E was accelerated with increasing concentrations of aggregated LDL and was accompanied by an increase in the susceptibility of these foam cells to succumb to the cell lytic effects of oxidized LDL (OxLDL). However, vitamin E supplementation did not protect macrophages or foam cells from OxLDL-mediated cell lysis, suggesting that vitamin E loss in foam cells is not the cause of their increased susceptibility to cell lysis. Our results suggest that the beneficial effects of vitamin E on cardiovascular disease observed in humans are due neither to a reduction in the propensity of macrophages to form foam cells nor to an increased resistance of these cells to cytolytic OxLDL.

Key Words: vitamin E • oxidized LDL • macrophages • foam cells • cell death

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