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

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Cell Stress and Chaperones Aims and scope

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.

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Acknowledgments

We thank Rajam Csordas-Iyer for critical reading and editorial assistance. This work was supported by the European Initiative to Fight Chlamydial Infections by Unbiased Genomics (ECIBUG; # 818496 to GW), the Austrian Research Fund (FWF grant # 14741 to GW), and the TOLERAGE Health Research Grant (HEALTH-F4-2008-202156 to GW).

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  1. Adam Csordas

    Present address: Division of Cardiac and Vascular Surgery, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland

Authors and Affiliations

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

    Simone Kreutmayer, Adam Csordas, Giovanni Almanzar & Georg Wick

  2. Institute of Medical Microbiology, Hygiene and Infectious Diseases, Paracelsus Medical Private University of Salzburg, Salzburg, Austria

    Jan Kern, Viola Maass & Matthias Maass

  3. Biooptics Facility, Division of Neurobiochemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria

    Martin Offterdinger

  4. Division of Visceral, Transplant and Thorax Surgery, Innsbruck Medical University, Innsbruck, Austria

    Robert Öllinger

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  1. Simone Kreutmayer
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Correspondence to Adam Csordas.

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Simone Kreutmayer and Adam Csordas contributed equally to this work.

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Kreutmayer, S., Csordas, A., Kern, J. et al. 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 and Chaperones 18, 259–268 (2013). https://doi.org/10.1007/s12192-012-0378-7

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  • DOI: https://doi.org/10.1007/s12192-012-0378-7

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