Infectious agents and atherosclerosis: current perspectives and unsolved issues

The large amount of data accumulated in recent years has reinforced the idea that infectious agents may play a significant role in the pathogenesis of atherosclerosis and in the clinical manifestations of vascular disease. Seroepidemiological and experimental data linking Herpesviridae and Chlamydia pneumoniae to atherosclerosis appear to be confirmed by a number of studies, while the available evidence regarding Helicobacter pylori is more conflicting, partly due to the fact that the interest in this agent is more recent. Infectious agents may influence atherogenesis through a number of mechanisms, ranging from cell lysis to the stimulation of adhesion molecule expression and cytokine production by infected cells. The development of atherosclerosis after an acute infection seems unlikely. Rather, it appears that a chronic, persistent form of infection, especially with Chlamydia pneumoniae, may favor those structural and proinflammatory changes in the vascular wall which are necessary for the formation of an atheroma. A persistent chlamydial infection is accompanied by an increased production of microbial heat shock protein 60, which may induce antigenic mimicry and a chronic inflammatory reaction in the vascular wall. Pharmacological trials have yielded conflicting indications regarding the hypothesis that treatment with macrolide antibiotics may limit the progression of vascular disease and the recurrence of cardiovascular events, although in a limited number of cases. However, antimicrobial drugs do not act specifically against a single infectious agent and more specific therapeutic agents would be needed in order to test a causative link between a single infectious agent and vascular disease.