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

Simone Kreutmayer; Adam Csordas; Jan Kern; Viola Maass; Giovanni Almanzar; Martin Offterdinger; Robert Öllinger; Matthias Maass; Georg Wick

doi:10.1007/s12192-012-0378-7

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

Cell Stress Chaperones. 2013 May;18(3):259-68. doi: 10.1007/s12192-012-0378-7. Epub 2012 Nov 29.

Authors

Simone Kreutmayer¹, Adam Csordas, Jan Kern, Viola Maass, Giovanni Almanzar, Martin Offterdinger, Robert Öllinger, Matthias Maass, Georg Wick

Affiliation

¹ Laboratory of Autoimmunity, Division of Experimental Pathophysiology and Immunology, Biocenter, Innsbruck Medical University, Peter-Mayr Strasse 4a, 6020, Innsbruck, Austria.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Atherosclerosis / complications
Atherosclerosis / metabolism
Atherosclerosis / microbiology
Atherosclerosis / pathology*
Blood Coagulation
Cell Adhesion Molecules / metabolism
Cell Membrane / metabolism
Chaperonin 60 / genetics
Chaperonin 60 / metabolism*
Chemokines / metabolism
Chlamydia Infections / complications
Chlamydia Infections / metabolism
Chlamydia Infections / microbiology
Chlamydia Infections / pathology*
Chlamydophila pneumoniae / physiology*
Down-Regulation
Early Growth Response Protein 1 / metabolism
Human Umbilical Vein Endothelial Cells / metabolism
Human Umbilical Vein Endothelial Cells / microbiology
Human Umbilical Vein Endothelial Cells / pathology*
Humans
Inflammation / complications
Inflammation / metabolism
Inflammation / microbiology
Inflammation / pathology*
Inflammation Mediators / metabolism
Microscopy, Confocal
Mitochondrial Proteins / genetics
Mitochondrial Proteins / metabolism*
NADPH Oxidases / metabolism
Oxidative Stress*
Protein Transport
Reverse Transcriptase Polymerase Chain Reaction
Superoxide Dismutase / metabolism
Thioredoxins / metabolism
Up-Regulation

Substances

Cell Adhesion Molecules
Chaperonin 60
Chemokines
EGR1 protein, human
Early Growth Response Protein 1
HSPD1 protein, human
Inflammation Mediators
Mitochondrial Proteins
Thioredoxins
Superoxide Dismutase
NADPH Oxidases