From the Research Unit of Autoimmune Diseases, Department of Medicine B
(J.G., B.G., M.B., Y.L., A.A.-M., Y.S.); the Institute of Pathology (A.A.,
I.G., J.K.); and the Institute of Lipid and Atherosclerosis Research (H.L.,
A.S., D.H.), Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine,
Tel Aviv University, Israel.
Background—Immunization with
ß2-glycoprotein I (ß2GPI), 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 ß2GPI
immunization on the progression of atherosclerosis.
Methods and Results—In the first experiment, 3 groups of LDL
receptor–deficient (LDL-RD) mice (n=15 per group) were immunized with
either ß2GPI 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 (n=10 per group) were immunized similarly and fed an atherogenic
diet for 6 weeks. All ß2GPI-immunized mice developed high titers of
anti-ß2GPI antibodies as well as a specific lymph node proliferation
to ß2GPI. The average cholesterol levels did not differ
between the mice fed similar diets, regardless of the immunization
protocol. Atherosclerosis was enhanced in the
ß2GPI-immunized mice (mean aortic lesion, 26 000±5700
µm2) in comparison with their ovalbumin-immunized
(mean, 3000±1099 µm2; P<0.01) and
nonimmunized (mean, 2250±700 µm2;
P<0.01) littermates. The average lesion size in the
ß2GPI-immunized mice fed an atherogenic diet (mean,
98 000±8305 µm2) was larger than the
ovalbumin-immunized mice (mean, 81 250±12 933
µm2; P=NS) or the nonimmunized controls
(mean, 75 625±7281 µm2; P=NS). The
atherosclerotic plaques in the ß2GPI-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 ß2GPI
immunization and establish a new model for immune-mediated
atherosclerosis.
© 1998 American Heart Association, Inc.
Basic Science Reports
Induction of Early Atherosclerosis in LDL-Receptor–Deficient Mice Immunized With ß2-Glycoprotein I
Key Words: atherosclerosis • glycoproteins • antibodies • lipoproteins
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