Elsevier

The Lancet

Volume 341, Issue 8840, 30 January 1993, Pages 255-259
The Lancet

ARTICLES
Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis

https://doi.org/10.1016/0140-6736(93)92613-XGet rights and content

Abstract

Arteriosclerotic lesions can be induced in normocholesterolaemic rabbits by immunisation with heat-shock protein (hsp) 65, a stress protein expressed in high concentrations in human atherosclerotic lesions. If an immune reaction to hsp65 also plays a part in human atherogenesis, it should be possible to detect anti-hsp65 antibodies in patients with atherosclerotic lesions. To study the possible relation between immune reaction to hsp65 and atherosclerosis, 867 normal inhabitants of South Tyrol, aged 40-79 years, were selected randomly for determination of serum antibodies against hsp65, simultaneous sonographic assessment of carotid atherosclerotic lesions, and evaluation of established risk factors—ie, blood cholesterol, hypertension, smoking, diabetes mellitus, and obesity. Autoantibodies to nuclear antigens, thyroid antigens, and rheumatoid factors were also measured. Serum anti-hsp65 antibodies were significantly (p < 0·05) increased in subjects aged 60-79 years with carotid atherosclerosis compared with those without lesions, and increased antibody concentration was independent of age, sex, and other established risk factors. On the other hand, the incidence and titres of autoantibodies did not correlate with carotid atherosclerotic lesions. Our data provide the first evidence of a strong correlation between anti-hsp65 antibodies and carotid atherosclerosis, suggesting that hsp65 might be involved in the pathogenesis of atherosclerosis. Lancet 1993; 341: 255-59.

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      Importantly, they show that IgG and IgM antibodies against MDA-LDL are no longer associated with CV events if adjusted for total serum IgG and IgM levels, respectively. Human atherosclerosis is also associated with abundant expression of HSPs and elevated levels of anti-HSP65 in the serum [63]. Immunohistochemical methods have detected CD3+ T cells in both human coronary arteries and ruptured coronary plaques [64].

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