Apolipoprotein E and atherosclerosis: insight from animal and human studies

Major advances have been made in our understanding of the role of apolipopr otein E (apoE) in the onset and development of atherosclerosis. Increasing evidence from both animal and human studies suggests that apoE is able to p rotect against atherosclerosis by: a) promoting efficient uptake of triglyc eride-rich lipoproteins from the circulation; b) maintaining normal macroph age Lipid homeostasis; c) playing a role in cellular cholesterol efflux and reverse cholesterol transport; d) acting as an antioxidant; e) inhibiting platelet aggregation; and f) modulating immune function. In humans, apoE is polymorphic, and this genetic variation has a strong effect on its antiath erogenic characteristics. Thus, compared to the epsilon 3 allele, the epsil on 4 allele promotes atherosclerosis, whereas the epsilon 2 allele is eithe r pro- or anti-atherogenic, depending on the influence of both environmenta l and genetic factors. ApoE and its gene are prime targets for therapeutic intervention aimed at preventing or treating atherosclerotic vascular disea se. (C) 1999 Elsevier Science B.V. All rights reserved.