Hyperimmunization of apo-E-deficient mice with homologous malondialdehyde low-density lipoprotein suppresses early atherogenesis

Jacob George, Arnon Afek, Boris Gilburd, Hana Levkovitz, Aviv Shaish, Iris Goldberg, Yuri Kopolovic, Georg Wick, Yehuda Shoenfeld, Dror Harats*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

237 Scopus citations

Abstract

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 μm2 versus 158000 ± 12800 μm2; 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.

Original languageEnglish
Pages (from-to)147-152
Number of pages6
JournalAtherosclerosis
Volume138
Issue number1
DOIs
StatePublished - May 1998

Keywords

  • Antibodies
  • Apo-E
  • Atherosclerosis
  • Immune system
  • Lymphocytes
  • Malondialdehyde low-density lipoprotein
  • Mouse

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