Possibilities for therapeutic interventions in disrupting Chlamydophila pneumoniae involvement in atherosclerosis.
Strong sero-epidemiologic, pathologic, and experimental evidence suggests that Chlamydophila pneumoniae (Cpn) infection may play a causative role in the development of atherosclerosis. Cpn is an obligate intracellular gram-negative bacterium that is responsible for 10% of cases of community-acquired pneumonia. In addition to its presence in the respiratory tract, live Cpn has been found within atherosclerotic plaques. Experimental findings have established Cpn's ability to infect vascular cells and elicit important atherogenic responses. Furthermore, Cpn infection can promote atherosclerotic development in different animal models. To date however, large-scale antibiotic clinical trials have not been effective in preventing major cardiovascular events. It is becoming apparent that Cpn undergoes a persistent state of infection, which is refractory to current chlamydial antibiotics. New treatment strategies that are effective toward acute and persistent forms of Cpn infection are needed in order to effectively eradicate the bacterium within the vascular wall. Possible therapeutics targets include Cpn-specific proteins and machinery directly involved in their survival, replication and maintenance. Alternatively, selectively targeting host cell pathways and machinery required for Cpn's actions in vascular cells also represent potential treatment strategies for atherosclerosis.
Deniset
Justin F
JF
Department of Physiology, Faculties of Medicine and Pharmacy, Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.
Pierce
Grant N
GN
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D050197:Atherosclerosis / Q000150:complications* / Q000382:microbiology; D002690:Chlamydia Infections / Q000150:complications / Q000188:drug therapy*; D016993:Chlamydophila pneumoniae / Q000302:isolation & purification*; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D006801:Humans
D000900:Anti-Bacterial Agents