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. © 2011 bentham science publishers ltd.