PMID- 27062234
OWN - NLM
STAT- MEDLINE
DCOM- 20170727
LR  - 20180531
IS  - 1916-7075 (Electronic)
IS  - 0828-282X (Linking)
VI  - 32
IP  - 8
DP  - 2016 Aug
TI  - Regulating Inflammatory Immune Response to Atherogenic Antigens Prevents 
      Development and Progression of Atherosclerosis in New Zealand White Rabbits.
PG  - 1008.e1-1008.e10
LID - S0828-282X(15)01491-9 [pii]
LID - 10.1016/j.cjca.2015.09.022 [doi]
AB  - 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.
CI  - Copyright (c) 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All 
      rights reserved.
FAU - Philip, Sheena
AU  - Philip S
AD  - Mary and Gary Western and Tata Molecular Immunology Unit, Thrombosis Research 
      Institute, Bangalore, India.
FAU - Ponnusamy, Thiruvelselvan
AU  - Ponnusamy T
AD  - Manipal University at Thrombosis Research Institute, Bangalore, India.
FAU - Rao, Lakshmi Narasimha
AU  - Rao LN
AD  - Manipal University at Thrombosis Research Institute, Bangalore, India.
FAU - Biradar, Suryakant
AU  - Biradar S
AD  - Mary and Gary Western and Tata Molecular Immunology Unit, Thrombosis Research 
      Institute, Bangalore, India.
FAU - Kumar, Ramesh
AU  - Kumar R
AD  - Mary and Gary Western and Tata Molecular Immunology Unit, Thrombosis Research 
      Institute, Bangalore, India.
FAU - Deshpande, Vrushali
AU  - Deshpande V
AD  - Mary and Gary Western and Tata Molecular Immunology Unit, Thrombosis Research 
      Institute, Bangalore, India.
FAU - Lu, Xinjie
AU  - Lu X
AD  - Molecular Immunology Unit, Thrombosis Research Institute, London, United Kingdom.
FAU - Kakkar, Vijay V
AU  - Kakkar VV
AD  - Mary and Gary Western and Tata Molecular Immunology Unit, Thrombosis Research 
      Institute, Bangalore, India; Molecular Immunology Unit, Thrombosis Research 
      Institute, London, United Kingdom.
FAU - Mundkur, Lakshmi A
AU  - Mundkur LA
AD  - Mary and Gary Western and Tata Molecular Immunology Unit, Thrombosis Research 
      Institute, Bangalore, India. Electronic address: lakshmi.mundkur@triindia.org.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151022
PL  - England
TA  - Can J Cardiol
JT  - The Canadian journal of cardiology
JID - 8510280
RN  - 0 (Apolipoproteins B)
RN  - 0 (Bacterial Outer Membrane Proteins)
RN  - 0 (Chaperonin 60)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Elapid Venoms)
RN  - 0 (Peptide Fragments)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 141319-23-5 (mambin)
RN  - 9007-34-5 (Collagen)
RN  - EC 6.3.2.3 (Glutathione Synthase)
SB  - IM
MH  - Adaptive Immunity
MH  - Animals
MH  - Aorta/cytology
MH  - Apolipoproteins B/*administration & dosage
MH  - Atherosclerosis/*immunology/pathology
MH  - Bacterial Outer Membrane Proteins/*administration & dosage
MH  - Chaperonin 60/*administration & dosage
MH  - Chemokine CCL2/metabolism
MH  - Chlamydophila pneumoniae
MH  - Collagen/metabolism
MH  - Cytokines/blood
MH  - Disease Progression
MH  - Elapid Venoms
MH  - Glutathione Synthase/administration & dosage
MH  - Immune Tolerance/immunology
MH  - Lymph Nodes/cytology
MH  - Macrophages/metabolism
MH  - Myocytes, Smooth Muscle/cytology
MH  - Peptide Fragments/*administration & dosage
MH  - Plaque, Atherosclerotic/immunology/pathology
MH  - Rabbits
MH  - Spleen/cytology
MH  - T-Lymphocytes/metabolism
MH  - Vascular Cell Adhesion Molecule-1/metabolism
EDAT- 2016/04/12 06:00
MHDA- 2017/07/28 06:00
CRDT- 2016/04/11 06:00
PHST- 2015/08/06 00:00 [received]
PHST- 2015/09/02 00:00 [revised]
PHST- 2015/09/03 00:00 [accepted]
PHST- 2016/04/11 06:00 [entrez]
PHST- 2016/04/12 06:00 [pubmed]
PHST- 2017/07/28 06:00 [medline]
AID - S0828-282X(15)01491-9 [pii]
AID - 10.1016/j.cjca.2015.09.022 [doi]
PST - ppublish
SO  - Can J Cardiol. 2016 Aug;32(8):1008.e1-1008.e10. doi: 10.1016/j.cjca.2015.09.022. 
      Epub 2015 Oct 22.