Association between Bacterial Infection and Peripheral Vascular Disease: A Review.

There are an increasing number of data showing a clinically important association between bacterial infection and peripheral artery disease (PAD). Bacteria suspected of being involved in PAD pathogenesis are: periodontal bacteria, gut microbiota, Helicobacter pylori, and Chlamydia pneumoniae. Infectious agents may be involved in the pathogenesis of atherosclerosis via activation of a systemic or local host immunological response to contamination of extravascular tissues or the vascular wall, respectively. A systemic immunological reaction may damage vascular walls in the course of autoimmunological cross-reactions between anti-pathogen antibodies and host vascular antigens (immunological mimicry), pathogen burden mechanisms (nonspecific activation of inflammatory processes in the vascular wall), and neuroendocrine-immune cross-talk. Besides activating the inflammatory pathway, bacterial infection may trigger PAD progression or exacerbation by enhancement of platelet reactivity, by a stimulatory effect on von Willebrand factor binding, factor VIII, fibrinogen, P-selectin activation, disturbances in plasma lipids, increase in oxidative stress, and resistance to insulin. Local inflammatory host reaction and induction of atherosclerotic plaque progression and/or instability result mainly from atherosclerotic plaque colonization by microorganisms. Despite these premises, the role of bacterial infection in PAD pathogenesis should still be recognized as controversial, and randomized, controlled trials are required to evaluate the outcome of periodontal or gut bacteria modification (through diet, prebiotics, and probiotics) or eradication (using antibiotics) in hard and surrogate cardiovascular endpoints.