Serum soluble heat shock protein 60 is elevated in subjects with atherosclerosis in a general population

Background-Work from our laboratory has proven that increased titers of ant i-heat shock protein 60 (HSP60) antibodies are associated with atherosclero sis and that HSP60-reactive T-cells are present in atherosclerotic lesions. Recent studies from others demonstrated that HSP60 directly activates endo thelial cells and macrophages. Methods and Results-To explore the possibility that HSP60 exists in the cir culation, where it could exert its functions, we performed a population-bas ed study with 826 subjects aged 40 to 79 years. The following items were me asured 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 prote in, alpha(1)-antitrypsin, and ceruloplasmin) and markers of systemic inflam mation. Carotid atherosclerosis was assessed mice (1990 and 1995), and 15 o ther risk factors were evaluated. Our data show that levels of sHSP60 were significantly elevated in subjects with prevalent/incident carotid atherosc lerosis and that these levels were correlated with common carotid artery in tima/media thickness. Multiple logistic regression analysis documented thes e associations as independent of age, sex, and other risk factors. Interest ingly, sHSP60 was also correlated with anti-lipopolysaccharide, anti-Chlamy dia and anti-HSP60 antibodies, various markers of inflammation, and the pre sence of chronic infections. The risk of atherosclerosis associated with hi gh 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 bet ween sHSP60 and atherosclerosis, suggesting that sHSP60 may play important roles in activating vascular cells and the immune system during the develop ment of atherosclerosis.