Mucosal Tolerance to a Combination of ApoB and HSP60 Peptides Controls Plaque Progression and Stabilizes Vulnerable Plaque in Apobtm2SgyLdlrtm1Her-J MiceReport as inadecuate




Mucosal Tolerance to a Combination of ApoB and HSP60 Peptides Controls Plaque Progression and Stabilizes Vulnerable Plaque in Apobtm2SgyLdlrtm1Her-J Mice - Download this document for free, or read online. Document in PDF available to download.

Oral tolerance to auto antigens reduces the development of atherosclerosis in mouse models. However, the effect of immune tolerance to multiple self antigenic peptides in plaque progression and stabilization is not known. We studied the protective effect of mucosal tolerance to peptides from apolipoprotein B ApoB; 661–680 and heat shock protein 60 HSP60; 153–163, in combination with diet, in the prevention of atherosclerotic lesion progression and plaque stabilization in ApoBtm25gyLDLrtm1Her mice. We found that oral administration of five doses of a combination of ApoB and HSP60 peptides 20 µg-mice-dose induced tolerance to both the peptides and reduced early plaque development by 39.9% better than the individual peptides ApoB = 28.7%;HSP60 = 26.8%P<0.001. Oral tolerance to combination of peptides along with diet modification arrested plaque progression by 37.6% which was associated with increases in T-regulatory cell and transforming growth factor-β expression in the plaque and peripheral circulation. Reduced macrophage infiltration and tumor necrosis factor-α expression in the plaque was also observed. Tolerance with continued hypercholesterolemia resulted in 60.8% reduction in necrotic core area suggesting plaque stabilization, which was supported by reduction in apoptosis and increased efferocytosis demonstrated by greater expression of receptor tyrosine kinase Mer MerTK in the plaque. Tolerance to the two peptides also reduced the expression of matrix metalloproteinase 9, tissue factor, calprotectin, and increased its collagen content. Our study suggests that oral tolerance to ApoB and HSP60 peptide combination induces CD4+ CTLA4+ Tregs and CD4+CD25+Foxp3+ Tregs secreting TGF-β, which inhibit pathogenic T cell response to both peptides thus reducing the development and progression of atherosclerosis and provides evidence for plaque stabilization in ApoBtm25gyLDLrtm1Her mice.



Author: Lakshmi Mundkur , Rupak Mukhopadhyay , Sonia Samson, Meenakshi Varma, Dnyaneswar Kale, Daxin Chen, Sneha Shivaprasad, Hemapriya S

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents