Diet-induced hypercholesterolemia and atherosclerosis in heterozygous apolipoprotein E-deficient mice
van Ree, J.H.
van den Broek, W.J.A.A.
TNO Preventie en Gezondheid
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
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Hyperlipoproteinemia type 3
Mice, Inbred C57BL
Mice, Mutant Strains
Atherosclerosis, 111 (1), 25-37