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Secreted apolipoprotein E reduces macrophage‐mediated LDL oxidation in an isoform‐dependent way
Author(s) -
Mabile Laurence,
Lefebvre Chantal,
Lavigne Jacques,
Boulet Lucie,
Davig Jean,
LussierCacan Suzanne,
Bernier Lise
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10697
Subject(s) - apolipoprotein e , antioxidant , macrophage , gene isoform , chemistry , biochemistry , cholesterol , oxidative phosphorylation , lipoprotein , microbiology and biotechnology , in vitro , biology , medicine , disease , gene
As an inflammatory cell, the macrophage produces various oxidizing agents, such as free radical species. These can modify LDL as a secondary effect and doing so may favor atherogenic processes. Any molecule able to counteract these reactions would be of much benefit, especially if secreted by the macrophage itself at the lesion site. Such is the case for apolipoprotein E (apoE), which has been shown to exert antioxidant properties in some studies, mostly in relation to Alzheimer's disease. In this study, we assessed the antioxidant potential of the various isoforms of apoE (E2, E3, and E4) using a metal‐induced LDL oxidation system with exogenous recombinant apoE and an in vitro model of macrophage‐mediated LDL oxidation. We found that all three isoforms had an antioxidant capacity. However, whereas apoE2 was the most protective isoform in the cell‐free system, the opposite was observed in apoE‐transfected J774 macrophages. In the latter model, cellular cholesterol efflux was found to be more important with apoE2, possibly explaining the larger quantity of oxidative indices observed in the medium. It is proposed that the antioxidant property of apoE results from a balance between direct apoE antioxidant capacities, such as the ability to trap free radicals, and potentially pro‐oxidative indirect events associated with cholesterol efflux from cells. Our observations add to the therapeutic potential of apoE. However, they also suggest the need for more experiments in order to achieve careful selection of the apoE isoform to be targeted, especially in the perspective of apoE transgene use. © 2003 Wiley‐Liss, Inc.