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Immunization using an Apo B-100 related epitope reduces atherosclerosis and plaque inflammation in hypercholesterolemic apo E(-/-) mice
- Chyu, KY (author)
- Zhao, XN (author)
- Reyes, OS (author)
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- Babbidge, SM (author)
- Dimayuga, PC (author)
- Yano, J (author)
- Cercek, B (author)
- Shah, PK (author)
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- (creator_code:org_t)
- Elsevier BV, 2005
- 2005
- English.
- In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 338:4, s. 1982-1989
- Journal article (peer-reviewed)
Abstract
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Keyword
- atherosclerosis
- immunization
- mice
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- art (subject category)
- ref (subject category)
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- Chyu, KY
- Zhao, XN
- Reyes, OS
- Babbidge, SM
- Dimayuga, PC
- Yano, J
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- Cercek, B
- Nordin Fredrikso ...
- Nilsson, Jan
- Shah, PK
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- NATURAL SCIENCES
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- Lund University
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