Title
Diet-induced hypercholesterolemia and atherosclerosis in heterozygous apolipoprotein E-deficient mice
Author
van Ree, J.H.
van den Broek, W.J.A.A.
Dahlmans, V.E.H.
Groot, P.H.E.
Vidgeon-Hart, M.
Frants, R.R.
Wieringa, B.
Havekes, L.M.
Hofker, M.H.
TNO Preventie en Gezondheid
Publication year
1994
Abstract
Apolipoprotein (apo) E is a ligand for the receptor-mediated uptake of lipoprotein remnant particles. Complete absence of apo E in humans leads to a severe form of type III hyperlipoproteinemia. We have used targeted inactivation in murine embryonic stem cells, as also described by others, to specifically study the effects of heterozygous Apoe gene loss on the development of hyperlipidemia. After 6 weeks on a severe semi-synthetic atherogenic diet, heterozygous null mutants, with only one functional Apoe allele, developed hypercholesterolemia as compared with controls (10.1 mM vs. 4.7 mM serum cholesterol). Interestingly, serum cholesterol levels in female heterozygotes were doubled as compared with male heterozygotes (15.0 mM vs. 7.5 mM). On this diet, heterozygous apo E deficient mice also showed an increased susceptibility to atherosclerosis, depending on gender (mean lesion area per section of 9524 μm2 vs. 61388 μm2 for males and females, respectively), whereas wild-type mice displayed far fewer lesions (354 μm2 and 9196 μm2 for males and females, respectively). This study indicates that a subnormal expression-level of the Apoe gene leads to hypercholesterolemia and, consequently, to an increased susceptibility to the development of atherosclerosis. Chemicals/CAS: Apolipoproteins E; Cholesterol, 57-88-5; Cholesterol, Dietary; Lipids
Subject
Nutrition
Atherosclerotic plaques
Cholesterol-rich diets
Gene targeting
Hyperlipoproteinemia
Mouse model
Apolipoprotein e
Cholesterol
Nitric oxide
Animal experiment
Animal model
Animal tissue
Aorta
Cholesterol diet
Controlled study
Female
Heterozygosity
Histology
Hyperlipoproteinemia type 3
Male
Mouse
Aging
Apolipoproteins E
Arteriosclerosis
Blotting, Northern
Blotting, Western
Cholesterol
Diet, Atherogenic
Disease Susceptibility
Heterozygote
Hypercholesterolemia
Lipids
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
To reference this document use:
http://resolver.tudelft.nl/uuid:0b9bc828-c4d6-4801-8371-ee154cffc81d
DOI
https://doi.org/10.1016/0021-9150(94)90188-0
TNO identifier
232712
ISSN
0021-9150
Source
Atherosclerosis, 111 (1), 25-37
Document type
article