ApoB-100 and HSP60 peptides exert a synergetic role in inhibiting early atherosclerosis in immunized ApoE-null mice.

Abstract

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.

• Authors: Jingjing Li, Xiuyun Zhao, Shichao Zhang, Shengying Wang, Peng Du, Gaofu Qi
• Journal: Protein and peptide letters (Protein Pept Lett) Vol. 18 Issue 7 Pg. 733-40 (Jul 2011) ISSN: 1875-5305 [Electronic] Netherlands
• PMID: 21413922 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein B-100
• Apolipoproteins E
• Chaperonin 60
• Recombinant Fusion Proteins

Topics

• Animals
• Apolipoprotein B-100 (genetics, immunology, metabolism)
• Apolipoproteins E (deficiency, genetics)
• Atherosclerosis (immunology, prevention & control)
• CD4-Positive T-Lymphocytes (immunology)
• Chaperonin 60 (genetics, immunology, metabolism)
• Dendritic Cells (immunology)
• Electrophoresis, Polyacrylamide Gel
• Male
• Mice
• Mice, Knockout
• Recombinant Fusion Proteins (genetics, immunology, metabolism)