Comparison of Oral Tolerance to ApoB and HSP60 Peptides in Preventing Atherosclerosis Lesion Formation in Apob48−/Ldlr− Mice

Author:

Mundkur Lakshmi1,Mukhopadhyay Rupak2,Deshpande Vrushali1,Samson Sonia1,Tarate Sagar1,Varma Meenakshi1,Sneha T. S.1,Lu Xinjie3,Kakkar Vijay V.13

Affiliation:

1. Mary and Gary Western and Tata Molecular Immunology Unit, Thrombosis Research Institute, Bangalore, Karnataka 560099, India

2. Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur, Assam 784028, India

3. Molecular Immunology Unit, Thrombosis Research Institute, London SW3 6LR, UK

Abstract

Antigen-specific immune modulation is emerging as an attractive therapeutic option to prevent atherosclerosis. We compared the efficacy of oral administration of peptides derived from apolipoprotein B (ApoB; 661–680) and heat shock protein 60 (HSP60; 153–163), in the prevention of atherosclerotic lesion formation hyperlipidemic low density lipoprotein receptordeficient (LDLr−/−), apolipoprotein B-100 only (apoB100/100) mice model. Oral administration of peptides induced tolerance as seen by an increase in regulatory T cells in the peripheral immune system. Tolerance to ApoB peptide reduced plaque development by 28.7% (P<0.001) while HSP60 was effective in reducing lesion development by 26.8% in ApoB48/LDLr−/− mice. While tolerance to HSP60 resulted in increase in anti-inflammatory cytokines (IL10 and TGF-β), ApoB tolerance was effective in reducing the lipid deposition in the lesion. Our results suggest that the two peptides have distinct mechanisms of controlling the development of atherosclerosis in mice.

Funder

Thrombosis Research Institute, London and Bangalore

Publisher

Hindawi Limited

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