The role of the infectious agents in the pathogenesis and evolution of atherosclerosis.
Atherosclerosis is a chronic inflammatory process due to the endothelial reaction to stress risk factors, only some of which are known. Clinical and experimental observations have suggested that several infectious agents are involved in this process. These agents, particularly the germ Chlamydia pneumoniae, and their relationship to the atheromata are described. Two hypotheses concerning how these infectious agents act are suggested. Both hypotheses are based on the capacity of these agents to induce the production, by endothelial cells, of the so-called heat shock protein (HSP), one of whose characteristics is to provoke an immune system reaction: 1) induction of a cross immune reaction, due to "molecular mimicry", between the HSP of infectious origin and the one that is produced by the endothelium as a consequence of stress due to the risk factors; 2) infection of the endothelial cells, followed by the synthesis and exposure on their surface of the HSP and activation of innate immune surveillance. Numerous experimental studies have been performed and are still being performed with the aim of verifying the efficacy of antibiotic treatment in preventing or reducing the rate of acute cardiovascular events. The results are still inconclusive. Probably, to be effective, treatment should be started at an earlier age. Prevention through vaccination against the involved microorganisms and the consequent induction of immune tolerance toward the HSP is also being investigated. As the mechanisms of action of infectious agents are further clarified, effective therapeutic and preventive measures could be taken with important clinical spin-offs.
Blasi
Claudio
C
UO Centro Prevenzione e Cura del Diabete ASL RMB, 1(o) Distretto di Roma. clblasi@tin.it
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology* / Q000517:prevention & control; D001428:Bacterial Vaccines / Q000627:therapeutic use; D023521:Chlamydophila Infections / Q000150:complications*; D016993:Chlamydophila pneumoniae / Q000276:immunology; D002986:Clinical Trials as Topic; D042783:Endothelial Cells / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D007239:Infections / Q000150:complications* / Q000188:drug therapy; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D001428:Bacterial Vaccines; D006360:Heat-Shock Proteins