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

Abstract

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 epitopes 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.

• Authors: Kuang-Yuh Chyu, Xiaoning Zhao, Odette S Reyes, Stephanie M Babbidge, Paul C Dimayuga, Juliana Yano, Bojan Cercek, Gunilla Nordin Fredrikson, Jan Nilsson, Prediman K Shah
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 338 Issue 4 Pg. 1982-9 (Dec 30 2005) ISSN: 0006-291X [Print] United States
• PMID: 16288717 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein B-100
• Apolipoproteins B
• Apolipoproteins E
• Epitopes
• Cholesterol

Topics

• Adoptive Transfer
• Animals
• Apolipoprotein B-100
• Apolipoproteins B (immunology)
• Apolipoproteins E (deficiency)
• Atherosclerosis (pathology, prevention & control, therapy)
• Cholesterol (blood)
• Epitopes (immunology)
• Hypercholesterolemia (immunology, pathology)
• Immunization
• Immunotherapy, Adoptive
• Inflammation (therapy)
• Male
• Mice
• Spleen (cytology)