title: 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.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, PR China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Zhao
authors.forename: Shichao
authors.initials: S
authors.lastname: Zhang
authors.forename: Shengying
authors.initials: S
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Du
authors.forename: Gaofu
authors.initials: G
authors.lastname: Qi
mesh_terms: D000818:Animals; D053299:Apolipoprotein B-100 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D050197:Atherosclerosis / Q000276:immunology* / Q000517:prevention & control; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D053299:Apolipoprotein B-100; D001057:Apolipoproteins E; D018834:Chaperonin 60; D011993:Recombinant Fusion Proteins