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Updated: Aug 15, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Macrophage apolipoprotein E reduces atherosclerosis and prevents premature death in apolipoprotein E and scavenger
Hong Yu1, Wenwu Zhang, Patricia G Yancey
1Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-6300, USA.
Insights
Macrophage apolipoprotein E (apoE) rescues mice lacking apoE and scavenger receptor B1 (SR-BI) from lethal hypercholesterolemia and atherosclerosis. Restoring apoE in macrophages dramatically reduces cholesterol, prevents arterial plaque, and extends lifespan.
Area of Science:
- Cardiovascular Biology
- Atherosclerosis Research
- Lipid Metabolism
Background:
- Mice lacking apolipoprotein E (apoE) and scavenger receptor B1 (SR-BI) exhibit severe hypercholesterolemia, coronary atherosclerosis, and premature death.
- Understanding the role of macrophage-derived apoE in this severe phenotype is critical for developing targeted therapies.
Purpose of the Study:
- To investigate the therapeutic potential of macrophage-derived apoE in ameliorating the severe dyslipidemia and atherosclerosis in apoE(-/-)SR-BI(-/-) mice.
- To determine if restoring apoE expression in macrophages can rescue the lethal phenotype associated with combined apoE and SR-BI deficiency.
Main Methods:
- Bone marrow transplantation (BMT) was performed on lethally irradiated apoE(-/-)SR-BI(-/-) mice using either wild-type (WT) or DKO bone marrow.
- Probucol was administered to mitigate anemia and facilitate BMT success, then discontinued post-transplant.
- Serum lipid profiles, lipoprotein analysis, and aortic atherosclerosis quantification were conducted post-BMT.
Main Results:
- Mice receiving WT bone marrow (WT-->DKO) showed detectable serum apoE and a 70% reduction in cholesterol levels compared to DKO-->DKO controls.
- WT-->DKO mice exhibited significantly reduced aortic atherosclerosis (88-90% reduction) compared to DKO-->DKO mice.
- Lifespan was dramatically extended in WT-->DKO mice (>40 weeks) versus DKO-->DKO mice (≤8 weeks).
Conclusions:
- Macrophage-derived apoE effectively rescues the lethal phenotype of apoE(-/-)SR-BI(-/-) mice.
- Restoration of apoE in macrophages significantly improves lipid profiles and reduces atherosclerotic burden.
- Targeting macrophage apoE represents a promising therapeutic strategy for severe dyslipidemia and atherosclerosis.
Objective:
Mice null for both apolipoprotein (apo)E and scavenger receptor (SR)-BI (DKO) develop severe hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarction, and premature death. The current study examines the ability of macrophage apoE to improve the dyslipidemia, reduce atherosclerosis, and rescue the lethal phenotype of DKO mice.
Methods And Results:
Initially, bone marrow transplantation (BMT) was unsuccessful, because the DKO mice died from a rapidly fatal anemia 3 to 5 days after lethal irradiation. Therefore, probucol was used to rescue the DKO mice during BMT and was discontinued 2-weeks after BMT, allowing successful reconstitution with donor marrow. Twelve male apoE(-/-)SR-BI(-/-) mice fed 0.5% probucol in a chow diet were lethally irradiated and transplanted with either wild-type (WT) or DKO bone marrow. Two-weeks after BMT, apoE was detected in serum in WT-->DKO mice, and mean serum cholesterol levels were reduced by 70% versus DKO-->DKO mice. Lipoprotein profiles and HDL subpopulations in WT-->DKO mice were similar to apoE(+/+)SR-BI(-/-)-->DKO mice and resembled those of SR-BI(-/-) mice. In WT-->DKO mice, aortic atherosclerosis was reduced by 88% to 90% versus DKO-->DKO mice. Furthermore, the DKO-->DKO mice died &8 weeks after BMT, whereas WT-->DKO mice exhibited a life span >40 weeks after BMT.
Conclusions:
Macrophage apoE is able to rescue the lethal phenotype of apoE(-/-)SR-BI(-/-) mice by improving the dyslipidemia and dramatically reducing atherosclerotic lesion development.
