title: Nasal immunization with heat shock protein 65 attenuates atherosclerosis and reduces serum lipids in cholesterol-fed wild-type rabbits probably through different mechanisms.
abstract: In recent years atherosclerosis has proved to be associated with microbial infection, inflammation and autoimmunity. Conservative heat shock protein (HSP) 65/60 is a major autoantigen of atherosclerosis. In the current study, experiments were specifically designed to investigate whether a nasal immunization with HSP65 could attenuate atherosclerosis in a cholesterol-fed wild-type animal model and explore its influence on serum lipids. Wild-type rabbits were nasally treated with HSP65 10 times on alternate days. At the end of the experiment, the rabbits showed remarkably lightened lesions in aortas. The suppression of T cell proliferation, increase of IL-10 production and absence of related antibodies implied that a tolerance to HSP65 was successfully established. Simultaneously, the serum lipid levels were down-regulated significantly in this group. Further results of another group immunized with conjugated protein HSP65+CTB-P277 showed that the lipid reduction could also be achieved by an immunization without inducing tolerance. But this simple reduction of lipids could not eventually alleviate atherosclerosis. In conclusion, nasal administration of HSP65 can effectively attenuate atherosclerosis in cholesterol-fed wild-type rabbits primarily by inducing an unresponsive state of tolerance. The accompanying reduction of lipids, which probably results from a different immune mechanism other than tolerance, cannot ultimately prevent the development of atherosclerotic lesions alone.
authors.affiliation: Minigene Pharmacy Laboratory, School of Life Science and Technology, China Pharmaceutical University, Nanjing, PR China.
authors.forename: Qiyan
authors.initials: Q
authors.lastname: Xiong
authors.forename: Jianping
authors.initials: J
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Jin
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.forename: Taiming
authors.initials: T
authors.lastname: Li
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000276:immunology / Q000628:therapy*; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000276:immunology; D018834:Chaperonin 60; D018833:Chaperonins / Q000008:administration & dosage* / Q000276:immunology; D002772:Cholera Toxin / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology; D007108:Immune Tolerance; D007114:Immunization; D008055:Lipids / Q000037:antagonists & inhibitors / Q000097:blood*; D008297:Male; D010446:Peptide Fragments / Q000276:immunology; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D018834:Chaperonin 60; D006360:Heat-Shock Proteins; D008055:Lipids; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C074119:heat-shock protein 65, Mycobacterium; C095402:peptide 277, heat shock protein 60; D002772:Cholera Toxin; D018833:Chaperonins