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 epsilon3 allele, the epsilon4 allele promotes atherosclerosis, whereas the epsilon2 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.
Davignon
J
J
Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, Quebec, Canada.
Cohn
J S
JS
Mabile
L
L
Bernier
L
L
D000818:Animals; D001057:Apolipoproteins E / Q000097:blood* / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans
D001057:Apolipoproteins E