Ca. Reardon et al., Effect of immune deficiency on lipoproteins and atherosclerosis in male apolipoprotein E-deficient mice, ART THROM V, 21(6), 2001, pp. 1011-1016
To determine whether T cells and B cells influence lipid metabolism and ath
erosclerosis, we crossed apolipoprotein E-deficient (apoE degrees) mice wit
h recombination activating gene 2-deficient (RAG2 degrees) mice. Total plas
ma cholesterol levels were approximate to 20% higher in male apoE degrees m
ice compared with the apoE degrees RAG2 degrees mice at 8 weeks of age, and
plasma triglyceride levels were 2.5-fold higher in the apoE degrees mice e
ven when plasma cholesterol levels were similar. Male mice with plasma chol
esterol 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" mi
ce, compared with that in the immune-competent apoE degrees mice, was 81% a
nd 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-w
eek cholesterol levels between 300 and 399 mg/dL. In apoE"RAG2" mice, aorti
c 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 p
rofound effect of the immune system on plasma lipid homeostasis.