title: Heat shock protein antibody titers are reduced by statin therapy in dyslipidemic subjects: a pilot study.
abstract: Antibody titers to heat shock protein (Hsp)-60 and -65 are positively related to risk of vascular disease and cardiovascular endpoints. There are few data on the factors that regulate the levels of these antibodies. It is known that the statins have antiinflammatory and immunoregulatory properties. The authors examined the effects of 2 statins, simvastatin (Zocor) and atorvastatin (Lipitor) on antibody titers to Hsp-60, -65, and -70 in a group of dyslipidemic patients. Twenty patients attending a lipid clinic, and previously not receiving lipid-lowering treatment, were treated with 10 mg of simvastatin (n = 11) or atorvastatin (n = 9) for 4 months. An additional 14 patients were recruited from the same clinic at the same hospital as a control group. The medication of these latter patients was unaltered for 4 months and the same parameters were measured as for the statin group. Antibody titers to Hsp-60, -65, and -70 were measured by enzyme-linked immunosorbent assay and lipoprotein profile and highly sensitive serum C-reactive protein (CRP) were measured by routine methods before and after treatment. Pretreatment and posttreatment data were compared by paired t or Mann-Whitney tests. Overall statin treatment was associated with a significant reduction in median antibody titers to Hsp-60 (17.2%, p = 0.03), Hsp-65 (15.9%, p = 0.003) and Hsp-70 (8.3%, p = 0.006), but not in control patients. Both statins caused a reduction in median serum CRP concentrations (45% overall, p < 0.05), but significant changes were not observed in the control patients. The effects on Hsp antibody titers were not related to changes in serum CRP concentrations (p > 0.05). However, there was a significant correlation between changes in antibody titers to Hsp-60 vs Hsp-65 (p < 0.01), Hsp-60 vs Hsp-70 (p < 0.05), and Hsp-65 vs Hsp-70 (p < 0.001). Statin treatment was associated with a reduction in antibody titers to Hsp-60, -65, and -70. This reduction is not fully explained by the antiinflammatory effects of the statins but may be due to their other immunomodulatory properties.
authors.affiliation: Centre for Clinical Science and Measurement, School of Biomedical and Molecular Science, University of Surrey, Guildford, Surrey, UK.
authors.forename: M
authors.initials: M
authors.lastname: Ghayour-Mobarhan
authors.forename: D J
authors.initials: DJ
authors.lastname: Lamb
authors.forename: N
authors.initials: N
authors.lastname: Vaidya
authors.forename: C
authors.initials: C
authors.lastname: Livingstone
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: G A A
authors.initials: GA
authors.lastname: Ferns
mesh_terms: D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D001323:Autoantibodies / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000276:immunology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology*; D006538:Heptanoic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000276:immunology; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D013223:Statistics as Topic; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D001323:Autoantibodies; D008078:Cholesterol, LDL; D006360:Heat-Shock Proteins; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D011758:Pyrroles; D014280:Triglycerides; D002097:C-Reactive Protein; D000069059:Atorvastatin; D019821:Simvastatin