Effect of macrophage-derived mouse ApoE, human ApoE3-Leiden, and human ApoE2 (Arg158→Cys) on cholesterol levels and atherosclerosis in ApoE- deficient mice
van Eck, M.
van Dijk, K.W.
van Berkel, T.J.C.
Gaubius Instituut TNO
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
To reference this document use:
Low density lipoprotein
Cholesterol blood level
Bone Marrow Transplantation
Arteriosclerosis, Thrombosis, and Vascular Biology, 20 (1), 119-127