Regulating Inflammatory Immune Response to Atherogenic Antigens Prevents Development and Progression of Atherosclerosis in New Zealand White Rabbits.
Can J Cardiol
; 32(8): 1008.e1-1008.e10, 2016 08.
Article
em En
| MEDLINE
| ID: mdl-27062234
ABSTRACT
BACKGROUND:
Inflammatory immune response to atherogenic self-antigens plays an important role in the development of atherosclerosis. We evaluated the role of oral tolerance to three peptides in controlling atherosclerosis in New Zealand white rabbits.METHODS:
Peptides derived from apolipoprotein B (ApoB), heat shock protein 60, and outer membrane protein from Chlamydia pneumoniae were expressed as part of the dendroaspin protein scaffold (AHC). Groups of 3-month-old rabbits were dosed orally with purified AHC protein either before the onset of disease or 2 months after inducing atherosclerosis; they were euthanized at the age of 7 months to study disease development and progression.RESULTS:
Oral treatment with AHC resulted in a marked increase in regulatory T cells in the lymphoid organs and reduced the development and progression of atherosclerosis by 48.6% and 28.4%, respectively (P < 0.05). Oral tolerance decreased plaque inflammation, enhanced expression of anti-inflammatory and regulatory markers in the aorta, and attenuated the adaptive immune response to self-antigens. AHC treatment in rabbits with established disease significantly decreased vascular cell adhesion molecule 1 (VCAM-1) (6.2 fold) and monocyte chemoattractant protein-1(MCP-1) (3 fold) expression and reduced the infiltration of macrophages into the aorta. Collagen content and the smooth muscle cell-to-macrophage ratio were higher in treated animals, whereas markers of plaque vulnerability, including matrix metalloproteinase expression, were reduced.CONCLUSIONS:
Our results suggest that oral tolerance to multiantigenic AHC molecule restores the immune balance and induces markers of plaque stability in rabbits.
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Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas B
/
Fragmentos de Peptídeos
/
Proteínas da Membrana Bacteriana Externa
/
Chaperonina 60
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Aterosclerose
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article