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Immunization using an Apo B-100 related epitope reduces atherosclerosis and plaque inflammation in hypercholesterolemic apo E(-/-) mice

Author:
  • KY Chyu
  • XN Zhao
  • OS Reyes
  • SM Babbidge
  • PC Dimayuga
  • J Yano
  • B Cercek
  • Gunilla Nordin Fredrikson
  • Jan Nilsson
  • PK Shah
Publishing year: 2005
Language: English
Pages: 1982-1989
Publication/Series: Biochemical and Biophysical Research Communications
Volume: 338
Issue: 4
Document type: Journal article
Publisher: Elsevier

Abstract english

Immune system modulates atherosclerosis and immunization using homologous LDL reduces atherosclerosis in hyperlipidemic animals. The nature of athero-protective antigenic epitopes in LDL remains unclear. We have recently identified nearly a 100 antigenic epilopes in human apo B-100 and in this study we evaluated the effects of immunization with two such epitopes on atherosclerosis in hypercholesterolemic apo E (-/-) mice. Male apo E (-/-) mice were immunized at 6-7 weeks of age with two different apo B-100 related peptide sequences using alum as adjuvant and mice immunized with alum alone served as controls. Peptide-2 immunization reduced aortic atherosclerosis by 40% and plaque inflammation by 80% compared to controls without a reduction in circulating cholesterol levels whereas Peptide-1 immunization had no effect. Peptide-2 immunization also reduced the progression of aortic lesions when mice were immunized at 16 weeks of age, suggesting the possibility of immuno-modulation in treating established atherosclerosis. The athero-protective effect of Peptide-2 immunization was absent in splenectomized mice but could be conveyed to non-immunized mice via adoptive transfer of splenocytes from peptide-2 immunized mice. In conclusion, immunization with a specific apo B-100 related peptide sequence reduces aortic atherosclerosis and plaque inflammation. Such acquired immunity and athero -protective effect appears to be mediated by splenocytes. These data demonstrate the feasibility of peptide based immunomodulating therapy for atherosclerosis.

Keywords

  • Biological Sciences
  • atherosclerosis
  • immunization
  • mice

Other

Published
  • Cardiovascular Research - Immunity and Atherosclerosis
  • ISSN: 1090-2104
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

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