Molecular mimicry in atherosclerosis: a role for heat shock proteins in immunisation

Abstract

Atherosclerosis has long been recognised as having an inflammatory component, and this has a particularly important bearing on to its clinical complications as it may result in plaque instability. Results of recent epidemiological studies have reinforced the potential importance of this aspect of the disease. Positive associations have been reported between exposure to several specific pathogens, and future risk of coronary heart disease (CHD). Whilst it is possible that each individual organism contributes to this susceptibility by a different mechanism, it is more likely that one or more common mechanism(s) exist. One possible hypothesis is that an immune response mounted against antigens on pathogenic organisms cross-react with homologous host proteins in a form of 'molecular mimicry'. A group of protein candidates that may be implicated in this process are the stress-induced proteins collectively known as heat shock proteins (HSP). HSPs are expressed and/or secreted by several pathogens, principally Chlamydia pneumoniae and Helicobacter pylori, but are also elaborated by mammalian vascular cells exposed to the stress associated with reperfusion injury or acute hypertension. The HSPs are also expressed by cells within atherosclerotic plaques. Serum titres of anti-HSP antibodies have been reported to be positively related to future risk of CHD. In addition, purified anti-HSP antibodies recognise and mediate the lysis of stressed human endothelial cells and macrophages in vitro. Furthermore, immunisation with HSP exacerbates atherosclerosis in experimental animal models. Some human vaccines, such as BCG, contain HSPs, hence although vaccination programmes are vital for maintaining 'herd' immunity and the prevention of serious infectious disease, they may leave a legacy of increased susceptibility to atherosclerosis. Development of HSP-free vaccines could satisfy the twin goals of protection from infection and reduced incidence of coronary disease.