Published online before print June 5, 2003, doi: 10.1161/01.ATV.0000079793.58054.2E
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© 2003 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Genetic Background Selectively Influences Innominate Artery Atherosclerosis
Immune System Deficiency as a Probe
From the Department of Pathology, University of Chicago, Chicago, Ill.
Correspondence and reprint requests to Catherine A. Reardon, University of Chicago, Department of Pathology MC 1089, 5841 S Maryland Ave, Chicago, IL 60637. E-mail reardon{at}midway.uchicago.edu
Objective— We sought to examine whether there is a site-specific effect on atherosclerosis of the absence of mature T and B cells caused by a recombination activating-gene deficiency in LDL receptor-deficient mice and whether this effect is influence by the extent of backcrossing to C57BL/6 mice.
Methods and Results— Male mice were fed atherogenic diets for 3 months. In strain 1 mice, in which 
93% of the genes were from C57BL/6 mice, the absence of mature T and B cells led to a significant reduction in atherosclerosis in both the aortic sinus and the innominate artery. In strain 2 mice, in which 99+% of the genes were from C57BL/6 mice, immune system deficiency led to a site-specific effect on atherosclerosis, with a reduction in atherosclerosis in the aortic sinus but not in the innominate artery, similar to previous results obtained with apolipoprotein E-/- mice. All of the immune system-incompetent mice had lower plasma total and VLDL cholesterol levels regardless of strain or diet, indicating that differences in lipid levels were unlikely to be responsible for these site-specific effects of immune system deficiency.
Conclusions— These results suggest that immune system deficiency has a site-specific effect on atherosclerosis that is sensitive to the genetic background of the mice.
Key Words: atherosclerosis • LDL receptor deficiency • genetics • aortic sinus • innominate artery
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