Background-Immunization with ␤ 2 -glycoprotein I (␤2GPI), the probable target of autoimmune anticardiolipin antibodies, results in experimental antiphospholipid syndrome in different mouse strains. The present study was undertaken to evaluate the effect of ␤2GPI immunization on the progression of atherosclerosis. Methods and Results-In the first experiment, 3 groups of LDL receptor-deficient (LDL-RD) mice (nϭ15 per group) were immunized with either ␤2GPI or ovalbumin or were not immunized and were fed a chow diet for 12 weeks. In a second experiment, 3 groups of LDL-RD mice (nϭ10 per group) were immunized similarly and fed an atherogenic diet for 6 weeks. All ␤2GPI-immunized mice developed high titers of anti-␤2GPI antibodies as well as a specific lymph node proliferation to ␤2GPI. The average cholesterol levels did not differ between the mice fed similar diets, regardless of the immunization protocol. Atherosclerosis was enhanced in the ␤2GPI-immunized mice (mean aortic lesion, 26 000Ϯ5700 m 2 ) in comparison with their ovalbumin-immunized (mean, 3000Ϯ1099 m 2 ; PϽ0.01) and nonimmunized (mean, 2250Ϯ700 m 2 ; PϽ0.01) littermates. The average lesion size in the ␤2GPI-immunized mice fed an atherogenic diet (mean, 98 000Ϯ8305 m 2 ) was larger than the ovalbumin-immunized mice (mean, 81 250Ϯ12 933 m 2 ; PϭNS) or the nonimmunized controls (mean, 75 625Ϯ7281 m 2 ; PϭNS). The atherosclerotic plaques in the ␤2GPI-immunized mice appeared to be more mature, and denser infiltration of CD4 lymphocytes was present in the subendothelium of the aortic sinuses from this group of mice. Conclusions-The results of the present study provide the first direct evidence for the proatherogenic effect of ␤2GPI immunization and establish a new model for immune-mediated atherosclerosis. (Circulation. 1998;98:1108-1115.)

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