Title
Effect of macrophage-derived mouse ApoE, human ApoE3-Leiden, and human ApoE2 (Arg158→Cys) on cholesterol levels and atherosclerosis in ApoE- deficient mice
Author
van Eck, M.
Herijgers, N.
van Dijk, K.W.
Havekes, L.M.
Hofker, M.H.
Groot, P.H.E.
van Berkel, T.J.C.
Gaubius Instituut TNO
Publication year
2000
Abstract
The effect of monocyte/macrophage-derived wild-type mouse apolipoprotein E (apoE), human apoE3-Leiden, and human apoE2 on serum cholesterol levels and the development of atherosclerosis in apoE-deficient (apoe-/-) mice was investigated by using bone marrow transplantation (BMT). At 4 weeks after BMT, murine apoe+/+ bone marrow reduced serum cholesterol levels by 87% in apoe-/- mice, whereas macrophage-derived human apoE3-Leiden and human apoE2 induced a maximal, transient reduction of 35% and 48%, respectively. At 4 months after BMT, atherosclerosis was 23-fold (P<0.001) reduced in apoe+/+→apoe-/- mice, whereas no significant reduction in apoE3-Leiden.apoe- /-→apoe-/- and apoE2.apoe-/-→apoe-/- mice could be demonstrated. A highly significant decrease in serum cholesterol levels (78% reduction) and atherosclerosis (21-fold, P<0.001) was found in apoE3-Leiden.apoe-/- animals expressing high levels of apoE in multiple tissues, whereas apoE2 was ineffective even at high concentrations. Furthermore, in contrast to apoE- deficient macrophages, cholesterol efflux from apoE2 or apoE3-Leiden macrophages was not impaired. In conclusion, apoE3-Leiden as well as apoE2 are less effective in reducing cholesterol levels and atherosclerosis in apoe-/- animals, compared with apoe+/+, with apoE2
Subject
Atherosclerosis
Hyperlipidemia
Low density lipoprotein
Animal model
Animal tissue
Cholesterol blood level
Cholesterol transport
Mouse
Nonhuman
Transgenic mouse
Animals
Apolipoprotein E2
Apolipoprotein E3
Apolipoproteins E
Arteriosclerosis
Bone Marrow Transplantation
Cholesterol
Humans
Liver
Macrophages, Peritoneal
Mice
Mice, Knockout
Mice, Transgenic
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http://resolver.tudelft.nl/uuid:48e0384e-a518-4620-a0ae-67586148a991
TNO identifier
235394
ISSN
1079-5642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 20 (1), 119-127
Document type
article