ApoB-100 and HSP60 Peptides Exert a Synergetic Role in Inhibiting Early Atherosclerosis in Immunized ApoE-null Mice
Human heat shock protein 60 (hHSP60) and apolipoprotein B-100 (ApoB-100) in oxidized low density lipoproteins are considered pro-atherosclerotic factors by inducing autoimmunity response, and immunization with peptides from these two proteins can inhibit atherosclerosis in animal models. In this study, we constructed chimeric proteins containing ApoB-100 and/or hHSP60 peptides by human intestinal trefoil factor (ITF) as a scaffold and then fused with glutathionine- S transferase (GST) for expression in Escherichia coli. These purified chimeric proteins were used for immunizing apolipoprotein E (ApoE)-null mice fed on Western diet, and then the immune response and anti-atherosclerotic effect was assayed. Unexpectedly, neither anti-ApoB-100 nor anti-hHSP60 antibodies could be detected in serum. Histological analysis demonstrated the mice immunized with a chimeric protein containing both ApoB-100 and hHSP60 peptides showed the most significant reduction of atherosclerotic lesions (65.9%), and the mice immunized with the chimeric protein only containing ApoB-100 or hHSP60 peptide also showed a 26.7% (p<0.01) or 61.5% (p<0.001) reduction of atherosclerotic lesions when compared to GST control. The chimeric protein containing hHSP60 peptide was more efficient than that containing apoB-100 peptide for inhibiting atherosclerosis. This result was further supported by the in vitro assay that hHSP60 peptide could induce DCs and CD4+ T cells to produce more TGF-beta (p<0.01) and less IFN-gamma (p<0.001) than ApoB-100 peptide. This result highlights a way for developing anti-atherosclerotic agents by construction of chimeric proteins containing hHSP60 and/or ApoB-100 peptides in the future.
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Document Type: Research Article
Publication date: 2011-07-01
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- Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.