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.

Effect of Cardiac Rehabilitation and Statin Treatment on Anti-HSP Antibody Titers in Patients With Coronary Artery Disease After Percutaneous Coronary Intervention

“…We also found that there was an association between anti-HSP60 antibody titers and anti-HSP70 antibody titers, although the association was weak. This finding supports the recent results from Ghayour-Mobarhan, et al, 15) but is in conflict with the results reported by Kocsis, et al who found that there was no association between the titers of HSP70 antibody and either the anti-HSP60 or anti-HSP65 titer. 29) It is interesting to learn that there was no relation between antibody titers to HSPs and other inflammatory factors, ie, hsCRP and IL-6 (data not shown).…”

“…Our results conflicted with those of Ghayour-Mobarhan and colleagues who reported that statin treatment was associated with a reduction in antibody titers to HSP60, HSP65, and HSP70. 15) We believe that this discrepancy may be explained by the underlying differences in the nature of the subjects. The subjects in this study were patients who had undergone revascularization (PCI) and were previously treated with lipid-lowering medication during the acute-phase (7-10 days).…”

Joint Effects of Antibody to Heat Shock Protein 60, Hypertension, and Diabetes on Risk of Coronary Heart Disease in Chinese

“…It is known that the statins have antiinflammatory, antioxidant, and immunoregulatory properties (26,27 ). GhayourMobarhan et al (28 ) first reported that statin treatment was associated with a significant reduction in median antibody concentrations to Hsp60, Hsp65, and Hsp70 in dyslipidemic subjects.…”

Heat shock proteins (HSPs) in the homeostasis of regulatory T cells (Tregs)

“…More and more attention is being paid to the role of the immune system in the pathogenesis of atherosclerosis because CD4 + T-cells and macrophages were found to be involved in its development. HSPs released from damaged cells during inflammatory response are particularly important autoantigens, which are assigned to the development of atherosclerotic plaques [60, 61]. In an animal model, the presence of specific HSP60 was demonstrated in the spleen and lymph nodes in both B and T lymphocytes, which was suggested to confirm autoimmune stimulation by HSP60 and indicate the role of HSP60 as a stimulator of the immune system in the development of atherosclerosis [62–65].…”