Atherosclerosis in C3H/HeJ mice reconstituted with apolipoprotein E-null bone marrow

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.