出版社：American Society for Biochemistry and Molecular Biology
摘要：We have previously reported that the introduction of macrophage apoE into mice lacking both apoE and the LDL receptor (apoE −/ − /LDLR −/ − ) through bone marrow transplantation (apoE +/ + /LDLR −/ − → apoE −/ − /LDLR −/ − ) produces progressive accumulation of apoE in plasma without affecting lipid levels. This model provides a tool to study the effects of physiologically regulated amounts of macrophage apoE on atherogenesis in hyperlipidemic animals. Ten-week-old male apoE −/ − /LDLR −/ − mice were transplanted with either apoE +/ + /LDLR −/ − (n = 11) or apoE −/ − /LDLR −/ − (n = 14) marrow. Although there were no differences between the two groups in lipid levels at baseline or at 5 and 9 weeks after transplantation, apoE levels in the apoE +/ + LDLR −/ − → apoE −/ − /LDLR −/ − mice increased to 4 times the apoE levels of normal mice. This resulted in a 60% decrease in aortic atherosclerosis in the apoE +/ + /LDLR −/ − → apoE −/ − /LDLR −/ − compared with the apoE −/ − /LDLR −/ − → apoE −/ − /LDLR −/ − controls, (15,957 ± 1907 vs. 40,115 ± 8302 μm2 ± SEM, respectively). In a separate experiment, apoE +/ + /LDLR −/ − mice were transplanted with either apoE +/ + /LDLR −/ − or apoE −/ − /LDLR −/ − marrow and placed on a high-fat diet for 8 weeks. In the absence of macrophage apoE, lesion area was increased by 75% in the aortic sinus and by 56% in the distal aorta. These data show that physiologic levels of macrophage apoE in the vessel wall are anti-atherogenic in conditions of severe hyperlipidemia and can affect later stages of plaque development.
