Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1011-1016
© 2001 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Effect of Immune Deficiency on Lipoproteins and Atherosclerosis in Male Apolipoprotein E–Deficient Mice
From the Department of Pathology, University of Chicago, Chicago, Ill.
Abstract—To
determine whether T cells and B cells influence lipid
metabolism and atherosclerosis, we crossed
apolipoprotein E–deficient (apoE°) mice with recombination
activating gene 2–deficient (RAG2°) mice. Total plasma
cholesterol levels were 
20% higher in male apoE° mice
compared with the apoE°RAG2° mice at 8 weeks of age, and plasma
triglyceride levels were 2.5-fold higher in the apoE°
mice even when plasma cholesterol levels were similar. Male
mice with plasma cholesterol levels between 400 and 600
mg/dL at 8 weeks of age were euthanized at 27 and 40 weeks of age. The
aortic root lesion area in the apoE°RAG2° mice, compared with that
in the immune-competent apoE° mice, was 81% and 57% smaller at 27
and 40 weeks of age, respectively. In contrast, there was no difference
in the size of the brachiocephalic trunk lesions. Similar results were
obtained with mice euthanized at 40 weeks of age that had 8-week
cholesterol levels between 300 and 399 mg/dL. In
apoE°RAG2° mice, aortic root atherosclerosis was
more profoundly suppressed at lower cholesterol levels.
Thus, T and B cells and their products differentially influence the
development of atherosclerosis at different sites. We
also demonstrate a profound effect of the immune system on plasma lipid
homeostasis.
Key Words: atherosclerosis • apolipoprotein E • immune deficiency • T cells • lipoproteins
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