Chlamydophila pneumoniae Infection Leads to Smooth Muscle Cell Proliferation and Thickening in the Coronary Artery without Contributions from a Host Immune Response

Abstract

Chlamydophila pneumonia (C. pneumonia) infection has been associated with the progression of atherosclerosis. It remains unclear, however, whether C. pneumoniae in the absence of an immune response can alone initiate atherogenic events within a complex vessel environment. Left anterior descending coronary arteries isolated from porcine hearts were dissected and placed in culture medium for 72 hours before infection with C. pneumoniae. C. pneumoniae replicated within the arterial wall for the duration of the experiment (up to 10 days). A significant increase in chlamydial-HSP60 protein expression from day 2 to 10 post-infection (pi) indicated the presence of metabolically active C. pneumonia within infected vessels. Significant arterial thickening in infected coronary segments was observed by a considerable decrease in the ratio of lumen to total vessel area (48 ؎ 3% at day 4 pi versus 23 ؎ 3% at day 10 pi) and a significant increase in the ratio of media to luminal area (113 ؎ 16% at day 4 pi versus 365 ؎ 65% at day 10 pi). Structural changes were accompanied by an up-regulation of host HSP60 and proliferating cell nuclear antigen expression levels. Immunohistochemical staining confirmed proliferating cell nuclear antigen expression to be primarily localized within smooth muscle cells of the medial area. These results demonstrate that C. pneumoniae infection can stimulate arterial thickening in a complex vessel environment without the presence of a host immune response and further supports the involvement of HSP60 in this action.

Impact of seropositivity to Chlamydia pneumoniae and anti-hHSP60 on cardiovascular events in hemodialysis patients

“…Moreover, antihHSP60 antibodies were not related to CP infection, cardiovascular risk factors, or incidence of CVD. These data agree with a recent paper, which reports, in an ex vivo model on coronary artery, the ability of CP to induce arterial thickening without the presence of a host immune response to HSP60 (Deniset et al 2010). These findings let us suppose that anti-hHSP60 autoimmunity does not play a role in the pathogenesis of CP infection and CP-associated cardiovascular risk.…”

Possibilities for therapeutic interventions in disrupting Chlamydophila pneumoniae involvement in atherosclerosis

“…Further studies have also shown that Cpn infection leads to endothelial dysfunction and neotintima formation [47][48][49]. Importantly, we have recently demonstrated using a novel ex vivo porcine coronary artery model that Cpn can induce arterial thickening in the absence of a host immune response ( Figure 2) [50]. These findings again support a causative role for Cpn in the development of atherosclerosis.…”

Efficient tumorigenesis by mutation-induced failure to terminate microRNA-mediated adaptive hyperplasia

“…Vascular wall infection by Chlamydophila pneumonia induces SMC proliferation and elevates risk of coronary heart disease [267,268], and similar effects are suspected for vascular infection by Helicobacter pylori [269,270]. The DAH hypothesis predicts that SMC hyperplasia induced by vascular-wall bacterial infection is an example of P-type AH, which is mediated and sustained by an epigenetically maintained miRNA profile similar to that observed in hyperplastic SMCs [257], as can readily be tested using methods mentioned above.…”