Genetic Background Determines the Extent of Atherosclerosis in ApoE-Deficient Mice

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 19; no. 8; pp. 1960 - 1968
• Main Authors: Dansky, Hayes M, Charlton, Sherri A, Sikes, John L, Heath, Simon C, Simantov, Ronit, Levin, Lawrence F, Shu, Pei, Moore, Karen J, Breslow, Jan L, Smith, Jonathan D
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01-08-1999; Hagerstown, MD Lippincott
• Subjects: Animals; Apolipoprotein A-I - physiology; Apolipoprotein A-II - physiology; Apolipoproteins E - deficiency; Arteriosclerosis - blood; Arteriosclerosis - genetics; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Female; Genetic Predisposition to Disease; Lipoproteins - blood; Lipoproteins, HDL - blood; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Deficiency; Rodentia; Cardiovascular disease; Metabolic diseases; Lipids; Genetic determinism; Vascular disease; Vertebrata; Mammalia; Mouse; Apolipoprotein E; Animal; Atherosclerosis; Risk factor; Genetics; Dyslipemia
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/01.atv.19.8.1960

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.