title: Chlamydia pneumoniae and atherosclerosis: does the evidence support a causal or contributory role?
abstract: The intracellular bacterial pathogen Chlamydia pneumoniae causes respiratory tract infection and has been associated with atherosclerosis and coronary artery disease. Since atherosclerosis is a progressive disease and is considered to be a chronic inflammation of the artery vessel wall, the interaction of C. pneumoniae with cells of the vasculature that can result in a local inflammatory response is of paramount importance. In this essay we review the pathophysiology of atherosclerosis in the context of C. pneumoniae infection and present an integrated model that includes the involvement of C. pneumoniae in all stages of atherogenesis including initiation, inflammation, fibrous plaque formation, plaque rupture and thrombosis. We hypothesize that acute and persistent infection of professional immune cells (T-cells, monocytes and macrophages) and non-immune cells (endothelial cells and smooth muscle cells) contributes to a sustained inflammatory response mediated by extensive cellular 'crosstalk' and numerous cytokines/chemokines. This cascade of inflammatory mediators may contribute to cellular dysfunction and tissue remodelling of the arterial intima. An improved understanding of the precise mechanism(s) of C. pneumoniae involvement in atherogenesis may help resolve the question of causality however, at the present time, we interpret the data as favoring a contributory rather than a causal role. Future research directed at the discovery of chlamydial virulence factors necessary for intracellular survival and subsequent alterations in host cell gene expression including signalling pathways may be important for the design of future clinical trials.
authors: Department of Pathology and Molecular Medicine, McMaster University, and the Father Sean O'Sullivan Research Center, St. Joseph's Hospital, 50 Charlton Ave. East, L8N 4A6, Hamilton, Ont., Canada. mahonyj@mcmaster.ca
authors: J B
authors: JB
authors: Mahony
authors: B K
authors: BK
authors: Coombes
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001161:Arteriosclerosis / Q000209:etiology* / Q000503:physiopathology*; D023521:Chlamydophila Infections / Q000150:complications* / Q000382:microbiology; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D051379:Mice; D011817:Rabbits
chemical_list: D000942:Antigens, Bacterial