(Circulation. 2000;102:14.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Serum Soluble Heat Shock Protein 60 Is Elevated in Subjects With Atherosclerosis in a General Population
From the Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck (Q.X., M.M., G.W.); the Department of Internal Medicine, University Hospital of Vienna (G.S.), Vienna, Austria; the Department of Neurology (J.W., S.K.), Institute for General and Experimental Pathology (H.P., G.W.), University of Innsbruck, Medical School, Innsbruck, Austria; and the Department of Internal Medicine, Hospital of Bruneck, Italy (G.E., F.O.).
Correspondence to Dr Qingbo Xu, Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, A-6020 Innsbruck, Austria. E-mail qingbo.xu{at}oeaw.ac.at
Background—Work from our laboratory has proven that increased titers of anti-heat shock protein 60 (HSP60) antibodies are associated with atherosclerosis and that HSP60-reactive T-cells are present in atherosclerotic lesions. Recent studies from others demonstrated that HSP60 directly activates endothelial cells and macrophages.
Methods and Results—To explore the possibility that HSP60
exists in the circulation, where it could exert its functions, we
performed a population-based study with 826 subjects aged 40 to 79
years. The following items were measured in all participants: serum
soluble HSP60 (sHSP60); anti-Escherichia coli
lipopolysaccharide; anti-HSP65,
anti-Chlamydia, and anti-Helicobacter
pylori antibodies; and a variety of acute phase reactants
(C-reactive protein, 
1-antitrypsin, and ceruloplasmin)
and markers of systemic inflammation. Carotid
atherosclerosis was assessed twice (1990 and 1995), and
15 other risk factors were evaluated. Our data show that levels of
sHSP60 were significantly elevated in subjects with prevalent/incident
carotid atherosclerosis and that these levels were
correlated with common carotid artery intima/media thickness. Multiple
logistic regression analysis documented these associations as
independent of age, sex, and other risk factors. Interestingly, sHSP60
was also correlated with anti-lipopolysaccharide,
anti-Chlamydia and anti-HSP60 antibodies, various
markers of inflammation, and the presence of chronic infections. The
risk of atherosclerosis associated with high sHSP60
levels was amplified when subjects had clinical and/or laboratory
evidence of chronic infections.
Conclusions—Our data provide the first evidence of a strong correlation between sHSP60 and atherosclerosis, suggesting that sHSP60 may play important roles in activating vascular cells and the immune system during the development of atherosclerosis.
Key Words: heat shock proteins • chaperonin 60 • aging • infection • inflammation • atherosclerosis
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