Stassen Frank R, Vainas Tryfon, Bruggeman Cathrien A
Department of Medical Microbiology and Maastricht Infection Center, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
Pharmacol Rep. 2008 Jan-Feb;60(1):85-92.
Already at the beginning of the 20th century, a potential role for microbes in vascular diseases was suggested. However, until the late '70 of that century, not much attention has been paid to this infection hypothesis. Then, predominantly based on the pioneering work of Fabricant et al., evidence for a contributing or even initiating role for microbes in atherosclerosis, as well as other vascular diseases, was accumulating. Also, the seminal paper by Saikku and co-workers, demonstrating serological evidence of an association of Chlamydia pneumoniae, an obligate intracellular respiratory gram-negative bacterium, with chronic coronary heart disease and acute myocardial infarction, significantly boosted the research on the infection hypothesis. Since then, numerous papers have been published demonstrating associations between a large variety of pathogens and atherosclerotic disease. Furthermore, many molecular mechanisms have been suggested by which microbes may affect atherogenesis. Nevertheless, in recent large randomised prospective trials, evaluating the efficacy of antibiotic treatment for the secondary prevention of coronary events, no reduction in the rate of cardiovascular events was observed, thereby seriously challenging the validity of the infection hypothesis. Nevertheless, the large body of supporting evidence, which has accumulate over the past decades, should not be ignored and maybe we should look at the hypothesis, and in particular the mechanisms by which microbes affect the disease, from a different angle.
早在20世纪初，就有人提出微生物在血管疾病中可能发挥作用。然而，直到那个世纪70年代末，人们对这种感染假说并未给予太多关注。随后，主要基于法布里坎特等人的开创性工作，微生物在动脉粥样硬化以及其他血管疾病中起促成甚至引发作用的证据不断积累。此外，赛库及其同事的开创性论文证明了肺炎衣原体（一种专性细胞内呼吸革兰氏阴性菌）与慢性冠心病和急性心肌梗死之间存在关联的血清学证据，这极大地推动了对感染假说的研究。从那时起，大量论文发表，证明了多种病原体与动脉粥样硬化疾病之间的关联。此外，人们还提出了许多微生物可能影响动脉粥样硬化发生的分子机制。然而，在最近评估抗生素治疗对冠心病事件二级预防疗效的大型随机前瞻性试验中，未观察到心血管事件发生率降低，从而严重质疑了感染假说的有效性。尽管如此，过去几十年积累的大量支持证据不应被忽视，也许我们应该从不同角度审视这一假说，尤其是微生物影响疾病的机制。
