Apolipoprotein AI transgene corrects apolipoprotein E deficiency-induced atherosclerosis in mice.
Apolipoprotein E (apo E)-deficient mice are severely hypercholesterolemic and develop advanced atheromas independent of diet. The C57BL/6 strain differs from most inbred strains by having lower HDL concentrations and a high risk of developing early atherosclerotic lesions when fed an atherogenic diet. The relative HDL deficiency and atherosclerosis susceptibility of the C57BL/6 strain are corrected with the expression of a human apolipoprotein AI (apo AI) transgene in this genetic background. To examine if increases in apo AI and HDL are also effective in minimizing apo E deficiency--induced atherosclerosis, we introduced the human apo AI transgene into the hypercholesterolemic apo E knockout background. Similar elevations of total plasma cholesterol occurred in both the apo E knockout and apo E knockout mice also expressing the human apo AI transgene. The latter animals, however, also showed a two- to threefold increase in HDL and a sixfold decrease in susceptibility to atherosclerosis. This study demonstrates that elevating the concentration of apo AI reduces atherosclerosis in apo E deficient-mice and suggests that elevation of apo AI and HDL may prove to be a useful approach for treating unrelated causes of heightened atherosclerosis susceptibility.
Life Sciences Division, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
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Pászty
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Maeda
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Verstuyft
E M
EM
Rubin
D000818:Animals; D016632:Apolipoprotein A-I / Q000032:analysis / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000097:blood / Q000628:therapy*; D005260:Female; D005838:Genotype; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D016632:Apolipoprotein A-I; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL