Differential effects of apolipoprotein E3 and E4 on markers of oxidative status in macrophages
ApoE is secreted by macrophages at the lesion site of the atherosclerotic plaque, where it is thought to play a protective role against atherosclerosis independently of its effects on lipid metabolism. Of the three common isoforms for apoE, apoE4 is associated with higher risk of cardiovascular dise...
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Published in | British journal of nutrition Vol. 97; no. 5; pp. 864 - 871 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Cambridge, UK
Cambridge University Press
01.05.2007
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Subjects | |
Online Access | Get full text |
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Summary: | ApoE is secreted by macrophages at the lesion site of the atherosclerotic plaque, where it is thought to play a protective role against atherosclerosis independently of its effects on lipid metabolism. Of the three common isoforms for apoE, apoE4 is associated with higher risk of cardiovascular disease (CVD). In vitro studies have shown that recombinant apoE may act as an antioxidant in an isoform-dependent manner (E2>E3>E4). The oxidative status of the macrophages plays a key role in the process of atherosclerosis. In the present study the possible differential actions of apoE3 and apoE4 on several parameters of oxidative status were determined in stably transfected murine macrophages (RAW 264·7-apoE3 and -apoE4). No differences between genotypes were observed after peroxide challenge in either protection against cytotoxicity or in cell membrane oxidation, and modest differences were observed in the non-enzymatic antioxidants (glutathione and α-tocopherol) in apoE3 v. apoE4 macrophages. Importantly, cells secreting apoE4 showed increased membrane oxidation under basal conditions, and produced more NO and superoxide anion radicals than the apoE3 macrophages after stimulation. The present data suggest that apoE genotype influences the oxidative status of macrophages, and this could partly contribute to the higher CVD risk observed in apoE4 carriers. |
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Bibliography: | ark:/67375/6GQ-NDNH5XTN-S ArticleID:66921 istex:A029B66CC1047F592E24ADEED02358F320F76870 PII:S0007114507669219 Abbreviations: AD, Alzheimer's disease; BSO, buthionine sulphoximine; GSH, reduced l-glutathione; LPS, lipopolysaccharide; PMA, phorbol myristate acetate |
ISSN: | 0007-1145 1475-2662 |
DOI: | 10.1017/S0007114507669219 |