title: Regulating Inflammatory Immune Response to Atherogenic Antigens Prevents Development and Progression of Atherosclerosis in New Zealand White Rabbits.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Our results suggest that oral tolerance to multiantigenic AHC molecule restores the immune balance and induces markers of plaque stability in rabbits.
authors.affiliation: Mary and Gary Western and Tata Molecular Immunology Unit, Thrombosis Research Institute, Bangalore, India.
authors.forename: Sheena
authors.initials: S
authors.lastname: Philip
authors.affiliation: Manipal University at Thrombosis Research Institute, Bangalore, India.
authors.forename: Thiruvelselvan
authors.initials: T
authors.lastname: Ponnusamy
authors.affiliation: Manipal University at Thrombosis Research Institute, Bangalore, India.
authors.forename: Lakshmi Narasimha
authors.initials: LN
authors.lastname: Rao
authors.affiliation: Mary and Gary Western and Tata Molecular Immunology Unit, Thrombosis Research Institute, Bangalore, India.
authors.forename: Suryakant
authors.initials: S
authors.lastname: Biradar
authors.affiliation: Mary and Gary Western and Tata Molecular Immunology Unit, Thrombosis Research Institute, Bangalore, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Mary and Gary Western and Tata Molecular Immunology Unit, Thrombosis Research Institute, Bangalore, India.
authors.forename: Vrushali
authors.initials: V
authors.lastname: Deshpande
authors.affiliation: Molecular Immunology Unit, Thrombosis Research Institute, London, United Kingdom.
authors.forename: Xinjie
authors.initials: X
authors.lastname: Lu
authors.affiliation: Mary and Gary Western and Tata Molecular Immunology Unit, Thrombosis Research Institute, Bangalore, India; Molecular Immunology Unit, Thrombosis Research Institute, London, United Kingdom.
authors.forename: Vijay V
authors.initials: VV
authors.lastname: Kakkar
authors.affiliation: Mary and Gary Western and Tata Molecular Immunology Unit, Thrombosis Research Institute, Bangalore, India. Electronic address: lakshmi.mundkur@triindia.org.in.
authors.forename: Lakshmi A
authors.initials: LA
authors.lastname: Mundkur
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001011:Aorta / Q000166:cytology; D001055:Apolipoproteins B / Q000008:administration & dosage*; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage*; D018834:Chaperonin 60 / Q000008:administration & dosage*; D018932:Chemokine CCL2 / Q000378:metabolism; D016993:Chlamydophila pneumoniae; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D004546:Elapid Venoms; D005981:Glutathione Synthase / Q000008:administration & dosage; D007108:Immune Tolerance / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D008264:Macrophages / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D010446:Peptide Fragments / Q000008:administration & dosage*; D058226:Plaque, Atherosclerotic / Q000276:immunology / Q000473:pathology; D011817:Rabbits; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001055:Apolipoproteins B; D001425:Bacterial Outer Membrane Proteins; D018834:Chaperonin 60; D018932:Chemokine CCL2; D016207:Cytokines; D004546:Elapid Venoms; D010446:Peptide Fragments; D019010:Vascular Cell Adhesion Molecule-1; C074772:mambin; D003094:Collagen; D005981:Glutathione Synthase