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

Chyu, KY; Zhao, XN; Reyes, OS; Babbidge, SM; Dimayuga, PC; Yano, J; Cercek, B; Nordin Fredrikson, Gunilla LU ; Nilsson, Jan LU and Shah, PK (2005) In Biochemical and Biophysical Research Communications 338(4). p.1982-1989
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 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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
atherosclerosis, immunization, mice
in
Biochemical and Biophysical Research Communications
volume
338
issue
4
pages
1982 - 1989
publisher
Elsevier
external identifiers
  • pmid:16288717
  • wos:000233815900045
  • scopus:27844435115
ISSN
1090-2104
DOI
10.1016/j.bbrc.2005.10.141
language
English
LU publication?
yes
id
70dd0531-edcd-4ec5-8ed3-b68486670818 (old id 211213)
date added to LUP
2007-08-15 09:44:59
date last changed
2017-08-06 04:40:03
@article{70dd0531-edcd-4ec5-8ed3-b68486670818,
  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 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.},
  author       = {Chyu, KY and Zhao, XN and Reyes, OS and Babbidge, SM and Dimayuga, PC and Yano, J and Cercek, B and Nordin Fredrikson, Gunilla and Nilsson, Jan and Shah, PK},
  issn         = {1090-2104},
  keyword      = {atherosclerosis,immunization,mice},
  language     = {eng},
  number       = {4},
  pages        = {1982--1989},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Immunization using an Apo B-100 related epitope reduces atherosclerosis and plaque inflammation in hypercholesterolemic apo E(-/-) mice},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2005.10.141},
  volume       = {338},
  year         = {2005},
}