Lamb David J, El-Sankary Wafaa, Ferns Gordon A A
Centre for Clinical Science and Measurement, School of Biomedical and Life Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
Atherosclerosis. 2003 Apr;167(2):177-85. doi: 10.1016/s0021-9150(02)00301-5.
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.
长期以来，动脉粥样硬化一直被认为具有炎症成分，这对其临床并发症具有特别重要的影响，因为它可能导致斑块不稳定。最近的流行病学研究结果强化了该疾病这一方面的潜在重要性。据报道，接触几种特定病原体与未来冠心病（CHD）风险之间存在正相关。虽然每种病原体可能通过不同机制导致这种易感性，但更有可能存在一种或多种共同机制。一种可能的假说是，针对致病生物体上抗原产生的免疫反应以“分子模拟”的形式与同源宿主蛋白发生交叉反应。一组可能与此过程有关的蛋白质候选物是统称为热休克蛋白（HSP）的应激诱导蛋白。HSP由几种病原体表达和/或分泌，主要是肺炎衣原体和幽门螺杆菌，但暴露于与再灌注损伤或急性高血压相关应激的哺乳动物血管细胞也会产生HSP。HSP也由动脉粥样硬化斑块内的细胞表达。据报道，抗HSP抗体的血清滴度与未来冠心病风险呈正相关。此外，纯化的抗HSP抗体在体外可识别并介导应激的人内皮细胞和巨噬细胞的裂解。此外，用HSP免疫会加剧实验动物模型中的动脉粥样硬化。一些人类疫苗，如卡介苗，含有HSP，因此尽管疫苗接种计划对于维持“群体”免疫力和预防严重传染病至关重要，但它们可能会留下对动脉粥样硬化易感性增加的后遗症。开发不含HSP的疫苗可以实现预防感染和降低冠心病发病率这两个目标。
