Effect of macrophage-derived apolipoprotein E on established atherosclerosis in apolipoprotein E-deficient mice

Apolipoprotein E-deficient (apoE(-/-)) mice have hyperlipidemia and develop spontaneous atherosclerosis in a time-dependent manner. Although macrophage-derived apoE has been shown to prevent the development of atherosclerosis in apoE(-/-) mice, whether it would induce regression of established atherosclerosis is unknown. To determine this, 8-week-old apoE(-/-) mice were transplanted with apoE(+/+) bone marrow. Four weeks after transplantation, when plasma cholesterol levels had reached normal levels, a group of mice (n= 12) were killed and their aortic lesions were measured and used as a baseline to judge regression. Twelve and 20 weeks after transplantation, aortic lesion areas of the mice were 9340±2184 μm² (mean±SEM, n=8) and 12 211 ±1433 μm² (n=9), respectively, values not significantly different from the lesion areas of the baseline mice (12 347±2487 μm²; n= 12, P>0.05). In contrast, apoE(-/-) mice reconstituted with apoE(-/-) bone marrow developed severe atherosclerotic lesions (453 036±29 767 μm², n=7) 20 weeks after transplantation. These data suggest that macrophage-derived apoE was insufficient to induce significant regression of established atherosclerotic lesions in apoE(-/-) mice, although it was sufficient to eliminate hypercholesterolemia and prevent progression of aortic lesions.