title: Immunization with a combination of ApoB and HSP60 epitopes significantly reduces early atherosclerotic lesion in Apobtm2SgyLdlrtm1Her/J mice.
abstract: OBJECTIVE
  HSP60 is emerging as an immunodominant target of autoantibodies in atherosclerosis and recent studies have revealed oxLDL as a key antigen in the development of atherosclerosis. In this study, we assay whether immunizing Apobtm2SgyLdlrtm1Her/J mice with a combination of ApoB and human HSP60 peptides has an additive effect on atheroprotection compared to ApoB or HSP60 peptides applied alone by following atherosclerotic lesion development.
  
  
  RESULTS
  In this study, 2 weeks after the first immunization, Apobtm2SgyLdlrtm1Her/J mice were placed on a high-fat diet for 8 weeks followed by 2 weeks on a normal diet allowing the mice to adapt to the environment before sacrifice. High levels of ApoB and HSP60 antibodies were detectable in week 2 and week 12 following the first immunization with KLH-conjugated ApoB and HSP60 peptides either individually or in combination. Histological analyses demonstrated that mice immunized with both, ApoB and HSP60 peptides, showed the most significant reduction in atherosclerotic lesions (41.3%; p<0.001) compared to a reduction of 14.7% (p<0.05) and 21.1% (p<0.01) in mice immunized with ApoB or HSP60 peptides, respectively; control mice were immunized with either PBS or adjuvant alone. These results were further supported by significant differences in the cellular and humoral immune responses between test animals.
  
  
  CONCLUSIONS
  Immunization with a combination of ApoB and HSP60 peptide antigens significantly reduced early atherosclerotic lesions in the Apobtm2SgyLdlrtm1Her/J mouse model of atherosclerosis. This approach offers promise as a novel strategy for developing anti-atherosclerotic agents.
authors.affiliation: Thrombosis Research Institute, London, United Kingdom. xlu@tri-london.ac.uk
authors.forename: Xinjie
authors.initials: X
authors.lastname: Lu
authors.forename: Daxin
authors.initials: D
authors.lastname: Chen
authors.forename: Valeria
authors.initials: V
authors.lastname: Endresz
authors.forename: Min
authors.initials: M
authors.lastname: Xia
authors.forename: Ildiko
authors.initials: I
authors.lastname: Faludi
authors.forename: Katalin
authors.initials: K
authors.lastname: Burian
authors.forename: Andrea
authors.initials: A
authors.lastname: Szabo
authors.forename: Agnes
authors.initials: A
authors.lastname: Csanadi
authors.forename: Andras
authors.initials: A
authors.lastname: Miczak
authors.forename: Eva
authors.initials: E
authors.lastname: Gonczol
authors.forename: Vijay
authors.initials: V
authors.lastname: Kakkar
mesh_terms: D000818:Animals; D053299:Apolipoprotein B-100 / Q000737:chemistry; D001055:Apolipoproteins B / Q000737:chemistry* / Q000235:genetics*; D050197:Atherosclerosis / Q000378:metabolism*; D001323:Autoantibodies / Q000737:chemistry; D018834:Chaperonin 60 / Q000737:chemistry*; D000939:Epitopes; D006801:Humans; D007107:Immune System; D056724:Immunity, Humoral; D007150:Immunohistochemistry / Q000379:methods; D008077:Lipoproteins, LDL / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000737:chemistry; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001323:Autoantibodies; D018834:Chaperonin 60; D000939:Epitopes; D008077:Lipoproteins, LDL; D010455:Peptides; D011973:Receptors, LDL