Prevalence of intimal heat shock protein 60 homologues in unstable angina and correlation with anti-heat shock protein antibody titers |
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Authors: | René P Andrié Gerhard Bauriedel Peter Braun Hans W Höpp Georg Nickenig Dirk Skowasch |
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Institution: | (1) Department of Internal Medicine II/Cardiology, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany;(2) Department of Cardiology, Hospital of Schmalkalden, Schmalkalden, Germany;(3) Department of Cardiology, Heart Center Duisburg, Duisburg, Germany;(4) Department of Cardiology, University of Cologne, Cologne, Germany |
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Abstract: | Heat shock proteins (HSPs) are among the most highly conserved and immunogenic proteins shared by microbial agents and mammals.
Human (h) HSP60 is upregulated under stress conditions and serves as a target for cross-reactive cytotoxic HSP-serum-antibodies.
The present study evaluates the expressions of hHSP60 and its homologue chlamydial (c) HSP60 in advanced human coronary lesions
and correlates intimal tissue-bound HSP expressions with circulating HSP-antibodies. Coronary atherectomy specimens retrieved
from 100 primary target lesions of patients with unstable angina (UA; n = 40) or stable angina (SA; n = 60) were assessed immunohistochemically for the presence of hHSP60 and cHSP60. In a subgroup (n = 40), blood samples were tested for anti-Chl. pn.-IgG/IgA-titers and anti-HSP65-antibody titers. Coronary plaques revealed immunoreactive hHSP60 in 55% and cHSP60 in 45% of
the lesions. Expression of both HSP homologues was significantly (each p < 0.001) higher in UA lesions compared with SA lesions (7.4 vs. 1.2% and 6.0 vs. 1.1%). HSP homologues showed positive correlations both in UA- and SA-lesions (r = 0.41, 0.33; p < 0.05). cHSP60 showed no association with anti-Chl. pn.-IgG/IgA-titers, whereas expressions of both homologues correlated positive with anti-HSP65-Ab titers (r = 0.42, p < 0.05; r = 0.50, p < 0.01). Intimal amounts of HSP60 homologues were associated with increased expressions of C-reactive protein, Toll-like
receptor-4 and tissue factor. Human and chlamydial HSP60 colocalize within coronary atheroma, most prevalent in lesions associated
with UA. Our data demonstrate a significant correlation between the intimal expressions of HSP60 homologues and serum HSP65
antibodies, thereby suggesting that humoral immune reactions may play an important role in coronary atherosclerosis and plaque
instability. |
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