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

Lakshmi Mundkur,Meenakshi Varma,T S Sneha,Rupak Mukhopadhyay,Xinjie Lu,Vijay V Kakkar,Vrushali Deshpande,Sagar Tarate,Sonia Samson

doi:10.1155/2013/212367

Lakshmi Mundkur, Meenakshi Varma + Show 7 more

Open Access

https://doi.org/10.1155/2013/212367

Copy DOI

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.

Highlights

Coronary artery disease remains the major cause of death and disability throughout the world despite the introduction of novel therapeutics [1]
Three days after oral dosing the number of CD4+CD25+ fox head box p3 (Foxp3)+ T cells increased significantly (P < 0.001) in payers patches (37.62% ± 3.09 versus 15.9% ± 1.54), spleen (28.4% ± 1.80 versus 9.44% ± 0.41), and in blood (26.23% ± 5.79 versus 4.50% ± 0.62) of heat shock protein 60 (HSP60)-treated animals compared to control
The increase in FoxP3 positive cells compared to control was maintained for 10 weeks after the oral dosing and was found to be significantly higher (P < 0.05) in the spleen (5.18% ± 0.91 and 4.48% ± 0.4 versus 2.25 ± 0.29) and blood (7.56% ± 0.68 and 5.11% ± 0.56 versus 2.28% ± 0.22) of apolipoprotein B (ApoB)- and HSP60-treated animals, respectively (Figure 1 and Supplementary Figure 2)

Summary

Introduction

Coronary artery disease remains the major cause of death and disability throughout the world despite the introduction of novel therapeutics [1]. Experimental observations in the past decade have proved that both innate and adaptive immune responses play an important role in the modulation of atherosclerosis. The complex role of the immune response in atherosclerosis is highlighted by the fact that they can contribute to both atheroprotective and proatherogenic effects [2,3,4]. The immune system generates regulatory T cells (Tregs), which actively suppress immune activation and maintain immune homeostasis [5, 6]. Treg cells with immunosuppressive properties is well established during the development of disease [7,8,9]. Antigenspecific immune modulation is emerging as an attractive therapeutic option to prevent inflammatory autoimmune diseases such as atherosclerosis [10,11,12]

Methods

Results

Conclusion