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Association of serum soluble heat shock protein 60 with toll-like receptor 4 polymorphism and severity of coronary artery disease
  1. K Mandal1,*,
  2. A R Afzal2,*,
  3. S J D Brecker2,
  4. J Poloniecki2,
  5. Q Xu2,
  6. M Jahangiri1
  1. 1Department of Cardiothoracic Surgery, St George’s Hospital Medical School, London, UK
  2. 2Department of Cardiac and Vascular Sciences, St George’s Hospital Medical School, London, UK
  1. Correspondence to:
    MissMarjan Jahangiri
    Department of Cardiothoracic Surgery, St George’s Hospital Medical School, London SW17 0QT, UK; marjan.jahangiri{at}stgeorges.nhs.uk

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Early atherosclerotic lesions are characterised by a relative abundance of inflammatory cells such as activated T lymphocytes, indicating involvement of immunoinflammatory process in the pathogenesis of atherosclerosis.1 One of the antigens stimulating recruitment of these T cells is believed to be heat shock protein (HSP). HSP60 (human) has been shown to enhance production of proinflammatory cytokines such as tumour necrosis factor α, interleukin 12, and interleukin 15 and to mediate monocyte adhesion to endothelial cells. In a large population based study, Xu et al2 have shown a correlation between soluble HSP60 (sHSP60) and the severity of carotid atherosclerosis. The association of sHSP60 in patients with coronary artery disease (CAD), however, remains to be clarified.

Human HSP60 has been shown to require functional toll-like receptor 4 (TLR4), a receptor involved in innate immunity, for stimulating production of tumour necrosis factor α and macrophages. Recently, two polymorphisms in the TLR4 gene, Thr399Ile and Asp299Gly, have been associated with lower concentrations of proinflammatory cytokines and a reduced extent or progression of carotid atherosclerosis.3

We hypothesised that serum sHSP60 would be associated with CAD and interact with TLR4 variants, determining the severity of prevalent CAD. The present study was designed to assess the association of sHSP60 with TLR4 polymorphisms with the severity of CAD.

METHODS

A prospective study of 329 consecutive patients admitted for elective coronary artery bypass graft surgery under the care of one surgical unit between August 2002 and November 2003 was carried out. The median age of the cohort was 65 years (range 40–80 years) with a male to female ratio of 4:1. Exclusion criteria were a recent history of myocardial infarction; unstable angina; infection; associated valvar heart disease; a history of inflammatory disorders, such as systemic lupus erythematosus; and use of immunosuppresive drugs such as steroids. The presence …

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