Chlamydia pneumoniae infection acts as an endothelial stressor with the potential to initiate the earliest heat shock protein 60-dependent inflammatory stage of atherosclerosis

Abstract

We identified increased expression and redistribution of the intracellular protein 60-kDa human heat shock protein (hHSP60) (HSPD1) to the cell surface in human endothelial cells subjected to classical atherosclerosis risk factors and subsequent immunologic cross-reactivity against this highly conserved molecule, as key events occurring early in the process of atherosclerosis. The present study aimed at investigating the role of infectious pathogens as stress factors for vascular endothelial cells and, as such, contributors to early atherosclerotic lesion formation. Using primary donor-matched arterial and venous human endothelial cells, we show that infection with Chlamydia pneumoniae leads to marked upregulation and surface expression of hHSP60 and adhesion molecules. Moreover, we provide evidence for an increased susceptibility of arterial endothelial cells for redistribution of hHSP60 to the cellular membrane in response to C. pneumoniae infection as compared to autologous venous endothelial cells. We also show that oxidative stress has a central role to play in endothelial cell activation in response to chlamydial infection. These data provide evidence for a role of C. pneumoniae as a potent primary endothelial stressor for arterial endothelial cells leading to enrichment of hHSP60 on the cellular membrane and, as such, a potential initiator of atherosclerosis.

Ateroesclerosis asociada a infección por chlamydophila pneumoniae: interacción entre el ser humano y una bacteria

“…También incrementa la concentración de moléculas de adhesión como: la molécula de adhesión leucocitaria tipo 1 (ELAM-1), molécula de adhesión intercelular tipo 1 (ICAM-1) y la molécula de adhesión de las células vasculares tipo 1 (VCAM-1) que permiten la migración de leucocitos y monocitos a través del endotelio vascular además, de varios de factores de crecimiento como el factor de crecimiento derivado de las plaquetas (PDGF), el factor nuclear-кβ (NF-кβ) que inducen el desarrollo de las células musculares lisas y producción de colágeno, fibrina y proteoglicanos por activación de las vías de la proteína cinasa activada por mitógenos ERK1/2MAPK o p44/p42 MAPK y de los receptores toll like receptors tipo 2 y tipo 4 ( TLR-2) y (TLR-4) 1,12,[16][17][18][19][20] .…”

Chlamydia pneumoniae Infection in Atherosclerotic Lesion Development through Oxidative Stress: A Brief Overview

“…Firstly, cHSP60 significantly increases superoxide anion production and decreases nitric oxide levels [93]. A further finding supporting the C. pneumoniae -mediated dysregulation of ROS-related enzymes comes from a recent study that has demonstrated the increased ROS production in infected endothelial cells through the up-regulation of NADPH oxidase (NOX-2 and NOX-4) and down-regulation of superoxide dismutase-1 (SOD-1) and thioredoxin-1 (TRX-1) [16]. …”

“…In fact, antioxidant treatment significantly reduced hHSP60 expression in response to C. pneumoniae infection [16]. In this regard, Wick et al [94] first suggested that the autoimmune reactions against hHSP60 may play a critical role in atherogenesis since both chlamydial and human HSP60 might mimic the ability of C. pneumoniae to stimulate the activation of vascular cells, leading to vascular endothelial injury.…”

“…C. pneumoniae infection has been shown to induce ROS production in all the cells involved in the atherosclerotic process such as macrophages, platelets, endothelial cells, and VSMCs leading to oxidative stress [13–16]. …”

Mannose-binding lectin 2 (Mbl2) gene polymorphisms are related to protein plasma levels, but not to heart disease and infection by Chlamydia

“…Several infectious agents represent important risk factors in the development of atherosclerosis (1,2); among them, Chlamydia pneumoniae in endothelial tissue has been strongly associated with coronary artery disease (CAD) (3 –6). Persistent C. pneumoniae infection may contribute to the development of atherosclerosis by stimulating the local immune response, possibly by triggering the chronic activation of inflammatory pathway components (7 –9).…”