Apolipoprotein E and atherosclerosis: insight from animal and human studies

Major advances have been made in our understanding of the role of apolipoprotein E (apoE) in the onset and development of atherosclerosis. Increasing evidence from both animal and human studies suggests that apoE is able to protect against atherosclerosis by: a) promoting efficient uptake of triglyceride-rich lipoproteins from the circulation; b) maintaining normal macrophage 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 antiatherogenic characteristics. Thus, compared to the epsilon 3 allele, the epsilon 4 allele promotes atherosclerosis, whereas the epsilon 2 allele is either pro- or anti-atherogenic, depending on the influence of both environmental and genetic factors. ApoE and its gene are prime targets for therapeutic intervention aimed at preventing or treating atherosclerotic vascular disease. (C) 1999 Elsevier Science B.V. All rights reserved.