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Atherosclerosis in C3H/HeJ mice reconstituted with apolipoprotein E-null bone marrow
Weibin Shi1, Xuping Wang, Khan Tangchitpiyanond
1Department of Radiology and Cardiovascular Research Center, University of Virginia, Charlottesville, USA.
Insights
Apolipoprotein E (apoE) deficiency in bone marrow did not increase atherosclerosis in resistant mice. ApoE promotes apolipoprotein B (apoB) accumulation in blood vessel walls.
Area of Science:
- Cardiovascular Biology
- Immunology
- Genetics
Background:
- Atherosclerosis susceptibility varies between mouse strains.
- Apolipoprotein E (apoE) plays a critical role in lipid metabolism and atherosclerosis.
- Previous studies indicated apoE-deficient bone marrow increases atherosclerosis in susceptible strains.
Purpose of the Study:
- To investigate the effect of apolipoprotein E-deficient (apoE(-/-)) bone marrow on atherosclerosis in an atherosclerosis-resistant mouse strain (C3H/HeJ).
- To determine if apoE deficiency in bone marrow impacts atherosclerosis development independently of plasma lipid levels.
Main Methods:
- Female C3H/HeJ mice underwent lethal irradiation and reconstitution with bone marrow from either C3H.apoE(-/-) or wild-type C3H mice.
- Mice were fed an atherogenic diet for 12 weeks post-transplantation.
- Plasma lipid profiles, apoE, and apolipoprotein B (apoB) levels in plasma and aortic walls were analyzed.
Main Results:
- Reconstitution with apoE(-/-) bone marrow led to a slight decrease in plasma apoE and a significant reduction of apoE and apoB in the aortic wall.
- Plasma apoB and cholesterol levels remained unchanged.
- No significant difference in atherosclerotic lesion size was observed at the aortic root between groups.
Conclusions:
- Bone marrow-derived apoE is not essential for determining atherosclerosis susceptibility in the C3H mouse strain.
- ApoE significantly contributes to the accumulation of apoB within the vessel wall, independent of systemic lipid levels.
Abstract:
Previous studies showed that reconstitution of atherosclerosis-susceptible C57BL/6 (B6) female mice with apolipoprotein E (apoE)-deficient (apoE(-/-)) bone marrow resulted in markedly increased atherosclerosis, despite the fact that plasma lipid levels were unchanged. To determine whether apoE(-/-) bone marrow would increase atherosclerosis in an atherosclerosis-resistant strain, female C3H/HeJ (C3H) mice were lethally irradiated and reconstituted with bone marrow from either C3H.apoE(-/-) mice or wild-type C3H mice. Four weeks after transplantation, the mice were fed an atherogenic diet for 12 weeks. We found that reconstitution of C3H mice with apoE(-/-) bone marrow resulted in a slight reduction in plasma apoE levels and a dramatic reduction in apoE and apolipoprotein B (apoB) in the aortic wall. Plasma apoB and cholesterol levels were unchanged, as were atherosclerotic lesions at the aortic root. These data indicate that reconstitution of C3H mice with apoE(-/-) bone marrow has no effect on atherosclerosis susceptibility and that apoE promotes accumulation of apoB in the vessel wall.