Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1960-1968
© 1999 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Genetic Background Determines the Extent of Atherosclerosis in ApoE-Deficient Mice
From the Laboratory of Biochemical Genetics and Metabolism (H.M.D., S.A.C., J.L.S., J.L.B., J.D.S.) and Laboratory of Statistical Genetics (S.C.H.), Rockefeller University, and the Division of Hematology-Oncology (R.S.) and Division of Cardiology (L.F.L.), Department of Medicine, Cornell University Medical College, New York, NY; and Millennium Pharmaceuticals, Inc (P.S., K.J.M.), Cambridge, Mass.
Correspondence to Jonathan D. Smith, Rockefeller University, Box 179, 1230 York Avenue, New York, NY 10021. E-mail smithj{at}rockvax.rockefeller.edu
Abstract—Two strains of ApoE-deficient mice were found to have markedly different plasma lipoprotein profiles and susceptibility to atherosclerosis when fed either a low-fat chow or a high-fat Western-type diet. FVB/NJ ApoE-deficient (FVB E0) mice had higher total cholesterol, HDL cholesterol, ApoA1, and ApoA2 levels when compared with C57BL/6J ApoE-deficient (C57 E0) mice. At 16 weeks of age, mean aortic root atherosclerotic lesion area was 7- to 9-fold higher in chow diet–fed C57 E0 mice and 3.5-fold higher in Western diet–fed C57 E0 mice compared with FVB E0 mice fed similar diets. Lesion area in chow diet–fed first-generation mice from a strain intercross was intermediate in size compared with parental values. The distribution of the lesion area in 150 chow diet–fed second-generation progeny spanned the range of the lesion area in both parental strains. There were no correlations between total cholesterol, non-HDL cholesterol, HDL cholesterol, ApoA1, ApoA2, ApoJ, or anti-cardiolipin antibodies and lesion area in the second-generation progeny. Thus, a genomic approach may succeed in identifying the genes responsible for the variation in atherosclerosis susceptibility in these 2 strains of ApoE-deficient mice, which could not be explained by measured plasma parameters.
Key Words: hypercholesterolemia • lipoproteins • apolipoproteins • intercross • oxidation
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