Title
Quantitative assessment of aortic atherosclerosis in APOE*3 leiden transgenic mice and its relationship to serum cholesterol exposure
Author
Groot, P.H.E.
van Vlijmen, B.J.M.
Benson, G.M.
Hofker, M.H.
Schiffelers, R.
Vidgeon-Hart, M.
Havekes, L.M.
Department of Vascular Biology, SmithKline Beecham Pharmaceuticals, Frythe, Welwyn, Hertfordshire, United Kingdom TNO-Prevention and Health, Gaubius Laboratory, Leiden, Netherlands SmithKline Beecham Pharmaceuticals, Frythe, Welwyn (Herts), AL6 9AR, United Kingdom TNO Preventie en Gezondheid
Publication year
1996
Abstract
Transgenic mice overexpressing the human dysfunctional apolipoprotein E variant, APOE*3 Leiden, develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. In the present study, we investigated the effects of diet composition and feeding period on serum cholesterol exposure and the amount of atherosclerosis in the aortic sinus in these mice, using quantitative image analysis. On each of the three diets tested-a low-fat diet, a high-saturated-fat/cholesterol diet, and a high saturated-fat/high- cholesterol/0.5%-cholate diet-transgenic animals showed a marked hyperlipidemia compared with nontransgenic littermates. Measurement of the atherosclerotic lesion areas in cross sections of the aortic sinus in animals exposed to these three diets for up to 6 months showed a 5 to 10 times greater lesion area in transgenic mice compared with nontransgenic controls. Highly significant positive correlations were found between the log-transformed data on lesion area and serum cholesterol exposure (r=.82 to .85 for the 1-, 2-, and 3-month treatment groups), indicating that the hyperlipidemia is likely to be a major determinant in lesion formation. On the basis of these findings, we suggest that the APOE*3 Leiden mouse represents a promising model for intervention studies with hypolipidemic and antiatherosclerotic drugs. Chemicals/CAS: apolipoprotein E3 (Leidein); Apolipoprotein E3; Apolipoproteins E; Cholesterol, 57-88-5; Cholesterol, Dietary; Dietary Fats
Subject
Biology
animal model
apolipoprotein E
diet
familial dyslipoproteinemia
hyperlipidemia
apolipoprotein e
cholesterol
animal experiment
animal model
animal tissue
aorta atherosclerosis
aorta sinus
article
atherosclerosis
cholesterol blood level
cholesterol diet
controlled study
dyslipoproteinemia
feeding
female
hyperlipidemia
hypolipemia
lipid diet
male
mouse
nonhuman
priority journal
transgenic mouse
Animals
Aortic Diseases
Apolipoprotein E3
Apolipoproteins E
Arteriosclerosis
Cholesterol
Cholesterol, Dietary
Dietary Fats
Female
Hyperlipidemias
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Sinus of Valsalva
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TNO identifier
233430
ISSN
1079-5642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 16 (8), 926-933
Document type
article