a1 Institute of Human Nutrition and Food Science, Christian Albrechts University of Kiel, Hermann-Rodewald-Strasse 6, 24098 Kiel, Germany
a2 Department of Plant Food Sciences and Technology, CSIC, Instituto del Frio, Jose Anotonio Novais 10, Ciudad Universitaria, Madrid, Spain
a3 School of Chemistry, Food and Pharmacy, University of Reading, Reading, RG6 6AP, UK
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.
(Received October 09 2006)
(Revised December 04 2006)
(Accepted December 05 2006)
Abbreviations: AD, Alzheimer's disease; BSO, buthionine sulphoximine; GSH, reduced l-glutathione; LPS, lipopolysaccharide; PMA, phorbol myristate acetate