Enhancement of atherosclerosis in beta-2-glycoprotein I-immunized apolipoprotein E-deficient mice

We have previously shown that low density lipoprotein receptor-deficient (L DL-RD) mice immunized with beta(2)-glycoprotein I (beta 2GPI; a target of a utoimmune anticardiolipin antibodies) developed enhanced early atherosclero sis, when fed a normal chow diet. The current study was undertaken to evalu ate the effect of immunization with beta 2GPI and the addition of a high fa t diet on the progression of atherosclerosis in the apolipoprotein E (ApoE) deficient mouse. Six-week-old female ApoE-deficient mice (n = 10) were immu nized subcutaneously with either human beta 2GPI or with ovalbumin, both em ulsified in complete Freund's adjuvant and fed a high fat diet for 6 weeks. The beta 2GPI-immunized mice were found to develop accelerated atheroscler osis when compared with their ovalbumin-immunized littermates (aortic lesio n area of 137,500 +/- 13,801 vs. 72,444 +/- 14,465 mu m(2), respectively; p = 0.0067). The beta 2GPI-immunized mice developed high liters of anti-beta 2GPI antibodies, 10 days after the procedure, which were sustained until t he sacrifice. LDL extracted from both study groups displayed similar suscep tibility to ex vivo oxidation. These results confirm our previous study in which we found increased atherosclerosis in beta 2GPI-immunized LDL-RD mice fed a chow diet. In the current study we show that the proatherogenic effe ct of beta 2GPI immunization is maintained despite high cholesterol levels and is not associated with increased susceptibility of LDL to ex vivo oxida tion.