Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1547-1559
Published online before print July 18, 2002, doi: 10.1161/01.ATV.0000029720.59649.50
Published online before print July 18, 2002, doi: 10.1161/01.ATV.0000029720.59649.50
© 2002 American Heart Association, Inc.
Brief Reviews |
Role of Heat Shock Proteins in Atherosclerosis
From the Department of Cardiological Sciences, St George’s Hospital Medical School, London, UK.
Correspondence to Prof Qingbo Xu, Department of Cardiological Sciences, St George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. E-mail q.xu{at}sghms.ac.uk
Heat shock proteins (HSPs) are present in most cells, serving as molecular chaperones, and they play a role in cell protection from damage in response to stress stimuli. However, accumulating data indicate the involvement of HSPs in the pathogenesis of diseases. The aim of this article is to update the progress concerning the role of HSPs in atherosclerosis. It has been demonstrated that HSPs are highly expressed in the atherosclerotic lesions of humans, rabbits, and apolipoprotein E–deficient mice. Risk factors for atherosclerosis, eg, infections, oxidized low density lipoprotein, oxidative stress, hypertension, and biomechanical stress, evoke HSP overexpression in endothelial cells, macrophages, and smooth muscle cells via activation of heat shock transcription factor 1. Interestingly, HSPs, normally localized within the cell, have been found as a soluble form in the blood, which is positively correlated with atherosclerosis in humans. Recently, several groups have reported that soluble HSPs specifically bind to the Toll-like receptor 4/CD14 complex, initiating an innate immune response, including the production of proinflammatory cytokines by macrophages and adhesion molecules in endothelial cells via nuclear factor-
B activation. Furthermore, the titers of autoantibodies against HSPs are significantly elevated in patients with atherosclerosis, and T lymphocytes specifically responding to HSPs have been found in atherosclerotic plaques. These proinflammatory responses and autoimmune reactions to HSPs in the vessel wall can contribute to the initiation and perpetuation of atherosclerosis. Thus, HSPs have a general role in the response of the arterial wall to stress and may serve as a mediator/inducer of atherosclerosis in particular circumstances.
Key Words: heat shock proteins • atherosclerosis • soluble heat shock proteins • proinflammatory response • autoimmunity
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