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 recently been the subject of intensive research. Several previous authors have put forward a paradigm of the autoimmune process occurring in the vicinity 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 atherogenesis in apo-E-deficient mice. Two groups of female chow-diet-fed, apo-E-deficient mice (n = 10) were either immunized with homologous MDA-LDL or with phosphate buffer saline (PBS) at 2-week intervals. The mice were sacrificed 12 weeks following the primary immunization. The MDA-LDL-immunized mice were shown to develop high titers of anti-MDA-LDL antibodies. Atherosclerosis, determined by the lesion size at the 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 microm2 versus 158000 +/- 12800 microm2; P < 0.01). No differences were found between the groups with respect to the cellular composition of the atherosclerotic plaques. The results of this study show that immunization with MDA-LDL has a protective effect in apo-E-deficient mice, and further suggests that this mouse model is suitable for studies of immunomodulation.
Department of Medicine B, Sheba Medical Center, Tel-Hashomer, Israel.
J
J
George
A
A
Afek
B
B
Gilburd
H
H
Levkovitz
A
A
Shaish
I
I
Goldberg
Y
Y
Kopolovic
G
G
Wick
Y
Y
Shoenfeld
D
D
Harats
D000818:Animals; D000906:Antibodies / Q000032:analysis; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D007114:Immunization; D007150:Immunohistochemistry; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000276:immunology*; D008315:Malondialdehyde / Q000276:immunology*; D051379:Mice; D012850:Sinus of Valsalva / Q000473:pathology
D000906:Antibodies; D001057:Apolipoproteins E; D008055:Lipids; D008077:Lipoproteins, LDL; D008315:Malondialdehyde