title: The magnitude of the immune response to heat shock protein-65 following BCG immunisation is associated with the extent of experimental atherosclerosis.
abstract: Several studies have reported associations between coronary heart disease (CHD) and infection. Recent studies have implicated immune responses to heat shock protein(s) (HSP) as a contributary factor. Using an immunisation model, we have assessed the relationship between the immune responses to HSP and subsequent atherosclerosis. Rabbits were immunised with bacillus Calmette-Guerin (BCG) vaccine (n=10) or saline (n=10) and subsequently fed a 0.25-1.0% cholesterol diet for 10 weeks. Plasma levels of IgG specific for mycobacterial antigen A60 and human HSP-60, but not for human HSP-70, rose following BCG immunisation, reaching a peak after 8 weeks. The percentage aortic area covered by atherosclerotic plaque was greater in animals immunised with BCG (30.5+/-3.8) compared to saline treated animals (16.4+/-2.6) (P<0.05). Furthermore, the individual titres of anti-HSP-60 in the BCG-immunised animal antibodies at week 8 (prior to starting the cholesterol diet) correlated with the percentage aortic area covered by plaque after 18 weeks (R2=0.72; P<0.05). No correlation was found between anti-A60 antibody titres and plaque area. Antiserum from BCG-immunised, but not control, animals stained heat-shocked endothelial cells. These data suggest that immune responses to HSP may be implicated in the relationship between specific infections and CHD.
authors.affiliation: Centre for Clinical Science and Measurement, School of Biomedical and Life Sciences, University of Surrey, Guildford, GU2 7XH, Surrey, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lamb
authors.forename: Gordon A A
authors.initials: GA
authors.lastname: Ferns
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001013:Aorta, Thoracic / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000276:immunology*; D001500:BCG Vaccine / Q000009:adverse effects / Q000097:blood / Q000276:immunology*; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018833:Chaperonins / Q000097:blood / Q000276:immunology*; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D003327:Coronary Disease / Q000209:etiology / Q000276:immunology / Q000473:pathology; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D007114:Immunization; D011817:Rabbits
chemical_list: D001500:BCG Vaccine; D001426:Bacterial Proteins; D018834:Chaperonin 60; D002791:Cholesterol, Dietary; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins