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Updated: Sep 29, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Physiological expression of macrophage apoE in the artery wall reduces atherosclerosis in severely hyperlipidemic
Sergio Fazio1, Vladimir R Babaev, Michael E Burleigh
1Vanderbilt University Medical Center, Departments of Medicine, Nashville, TN 37232, USA. sergio.fazio@vanderbilt.edu
Abstract:
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, (15957 +/- 1907 vs. 40115 +/- 8302 micro m(2) +/- 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.
Insights
Macrophage apolipoprotein E (apoE) significantly reduces atherosclerosis in hyperlipidemic mice. Introducing macrophage apoE lowered aortic plaque by 60%, demonstrating its anti-atherogenic role in severe hyperlipidemia.
Area of Science:
- Cardiovascular Research
- Atherosclerosis Research
- Lipid Metabolism
Background:
- Apolipoprotein E (apoE) plays a crucial role in lipid metabolism and transport.
- Macrophage-derived apoE's specific contribution to atherogenesis in hyperlipidemic conditions remains incompletely understood.
- Existing mouse models often lack physiologically regulated levels of macrophage apoE.
Purpose of the Study:
- To investigate the anti-atherogenic effects of physiologically regulated macrophage apoE in a murine model of severe hyperlipidemia.
- To determine if macrophage apoE influences the development and progression of atherosclerotic plaques.
Main Methods:
- Bone marrow transplantation was used to introduce macrophage-specific apoE expression in apoE(-/-)/LDLR(-/-) mice.
- Mice were transplanted with either apoE(+/+)/LDLR(-/-) or apoE(-/-)/LDLR(-/-) marrow.
- Atherosclerosis was quantified by measuring aortic lesion area in transplanted mice, some of which were fed a high-fat diet.
Main Results:
- Transplantation of apoE(+/+)/LDLR(-/-) marrow into apoE(-/-)/LDLR(-/-) mice led to a 4-fold increase in plasma apoE levels without altering lipid profiles.
- This resulted in a significant 60% reduction in aortic atherosclerosis compared to control mice lacking macrophage apoE.
- In a separate experiment, absence of macrophage apoE exacerbated lesion area by 75% in the aortic sinus and 56% in the distal aorta.
Conclusions:
- Physiologically relevant levels of macrophage apoE exert potent anti-atherogenic effects in the vessel wall.
- Macrophage apoE plays a critical role in mitigating atherosclerosis, even under conditions of severe hyperlipidemia.
- These findings highlight macrophage apoE as a potential therapeutic target for preventing or treating cardiovascular disease.
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