| Autor: |
Sergio Fazio, Vladimir R. Babaev, Michael E. Burleigh, Amy S. Major, Alyssa H. Hasty, MacRae F. Linton |
| Jazyk: |
angličtina |
| Rok vydání: |
2002 |
| Předmět: |
|
| Zdroj: |
Journal of Lipid Research, Vol 43, Iss 10, Pp 1602-1609 (2002) |
| Druh dokumentu: |
article |
| ISSN: |
0022-2275 |
| DOI: |
10.1194/jlr.M200108-JLR200 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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