HYPERIMMUNIZATION OF APO-E-DEFICIENT MICE WITH HOMOLOGOUS MALONDIALDEHYDE LOW-DENSITY-LIPOPROTEIN SUPPRESSES EARLY ATHEROGENESIS

The role of the immune system in modulating atherosclerosis has recent ly been the subject of intensive research. Several previous authors ha ve put forward a paradigm of the autoimmune process occurring in the v icinity of the plaque. Two recent studies have shown that immunization of rabbits with homologous modified low-density lipoprotein (LDL) led to suppression of atherosclerosis. In the current study we evaluated the effects of homologous malondialdehyde (MDA)-LDL immunizations on a therogenesis in apo-E-deficient mice. Two groups of female chow-diet-f ed, apo-E-deficient mice (n = 10) were either immunized with homologou s MDA-LDL or with phosphate buffer saline (PBS) at 2-week intervals. T he mice were sacrificed 12 weeks following the primary immunization. T he MDA-LDL-immunized mice were shown to develop high titers of anti-MD A-LDL antibodies. Atherosclerosis, determined by the lesion size at th e aortic sinus, was significantly suppressed in the MDA-LDL-immunized mice as compared with their littermates immunized with PBS (mean area +/- S.D.; 74000 +/- 17300 mu m(2) versus 158000 +/- 12800 mu m(2); P < 0.01). No differences were found between the groups with respect to t he cellular composition of the atherosclerotic plaques. The results of this study show that immunization with MDA-LDL has a protective effec t in apo-E-deficient mice, and further suggests that this mouse model is suitable for studies of immunomodulation. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.