European Heart Journal Advance Access originally published online on June 8, 2006
European Heart Journal 2006 27(13):1565-1570; doi:10.1093/eurheartj/ehl081
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Association between plasma levels of heat shock protein 60 and cardiovascular disease in patients with diabetes mellitus
1 Division of Microbial Diseases, UCL Eastman Dental Institute, University College London, 256 Gray's Inn Road, London WC1X 8LD, UK
2 Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free and University College London Medical School, London, UK
3 Department of Epidemiology and Public Health, University College London, 256 Gray's Inn Road, London WC1X 8LD, UK
4 Department of Cellular and Molecular Medicine, St George's University of London, London, UK
Received 16 December 2005; revised 8 May 2006; accepted 19 May 2006; online publish-ahead-of-print 8 June 2006.
* Corresponding author. Tel: +44 20 7915 1190; fax: +44 20 7915 1127. E-mail address: b.henderson{at}eastman.ucl.ac.uk
Aims Evidence is accumulating to support the hypothesis that the release of heat shock protein (Hsp)60 into the circulation is associated with the development of coronary heart disease (CHD). As diabetes is a risk factor for CHD, it was of interest to determine Hsp60 blood levels in a cross-sectional cohort of diabetic patients, some of whom had cardiovascular disease, and relate levels to relevant biochemical markers.
Methods and results A total of 855 patients with T1DM or T2DM, recruited as part of the UCL Diabetes and Cardiovascular disease Study (UDACS), were assayed for plasma levels of Hsp60. Immunoreactive Hsp60 was detected in 54% of the samples, with 26% having plasma levels >1 µg/mL. Levels of Hsp60 were higher in Caucasians than in other ethnic groupings, with 56.5% of Caucasian subjects, 37.5% of African-Caribbean subjects, and 47.1% of Indian subjects having detectable levels (P=0.007), and with a higher proportion of non-smokers having detectable Hsp60 levels than smokers (54.9 vs. 43.5%, P=0.01). Of note was the finding of an association between higher mean plasma levels of Hsp60 in subjects with clinically manifest cardiovascular disease and those with a history of myocardial infarction having an adjusted odds ratio of having detectable Hsp60 of 2.17 (CI 1.26–3.73).
Conclusion This is the first report of circulating Hsp60 levels in diabetic patients, which suggests that this secreted mitochondrial cell stress protein may be playing an unexpected role in the cardiovascular pathology associated with diabetes.
Key Words: Coronary disease • Chaperonin • Risk factor • Hsp60 • Myocardial infarction • UDACS
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