title: 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.
authors.affiliation: Laboratory of Autoimmunity, Division of Experimental Pathophysiology and Immunology, Biocenter, Innsbruck Medical University, Peter-Mayr Strasse 4a, 6020, Innsbruck, Austria.
authors.forename: Simone
authors.initials: S
authors.lastname: Kreutmayer
authors.forename: Adam
authors.initials: A
authors.lastname: Csordas
authors.forename: Jan
authors.initials: J
authors.lastname: Kern
authors.forename: Viola
authors.initials: V
authors.lastname: Maass
authors.forename: Giovanni
authors.initials: G
authors.lastname: Almanzar
authors.forename: Martin
authors.initials: M
authors.lastname: Offterdinger
authors.forename: Robert
authors.initials: R
authors.lastname: Öllinger
authors.forename: Matthias
authors.initials: M
authors.lastname: Maass
authors.forename: Georg
authors.initials: G
authors.lastname: Wick
mesh_terms: D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D001777:Blood Coagulation; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D002690:Chlamydia Infections / Q000150:complications / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D016993:Chlamydophila pneumoniae / Q000502:physiology*; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D018613:Microscopy, Confocal; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D021381:Protein Transport; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015815:Cell Adhesion Molecules; D018834:Chaperonin 60; D018925:Chemokines; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C060293:HSPD1 protein, human; D018836:Inflammation Mediators; D024101:Mitochondrial Proteins; D013879:Thioredoxins; D013482:Superoxide Dismutase; D019255:NADPH Oxidases