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Overexpression of MMP9 and Tissue Factor in Unstable Carotid Plaques Associated with Chlamydia pneumoniae, Inflammation, and Apoptosis

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Annals of Vascular Surgery

Abstract

Tissue remodeling by matrix metalloproteinases (MMPs) and plasminogen activators such as tissue factor (TF) is postulated to be involved in the pathogenesis of atherosclerosis. The in situ expression of MMP9 and TF in unstable atherosclerotic plaques has not been examined in detail. Moreover, interference of tissue remodeling by vascular inflammation, apoptosis, and Chlamydia pneumoniae inside plaque subregions is unclear. A total of 40 autopsy carotid arteries (controls) and 20 atherosclerotic carotid endarterectomy specimens (with type VI lesions, according to the American Heart Association classification) from stroke patients were analyzed for expression of MMP9 and TF using in situ techniques. The data on tissue remodeling were correlated with the presence of inflammatory cells (T cells, B-cells, macrophages), apoptosis, and the presence of C. pneumoniae using immunohistochemistry and Western blot analyses. We found a significant overexpression of MMP9 and TF in progressive atherosclerotic carotid arteries, especially in the shoulder and cap subregions (both p < 0.05). Expression of MMP9 and TF correlated significantly with T-cell and macrophage infiltrates as well as with apoptosis (p < 0.05). C. pneumoniae infection was significantly associated with elevated TF expression (p < 0.01) but not with MMP9. MMP9 and TF are thus significantly overexpressed in progressive atherosclerotic plaques, and their relevant subregions (shoulder and cap) are involved in plaque instability. This process is associated with local inflammatory cell infiltrates and apoptosis, which might be influenced by infectious agents such as C. pneumoniae.

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Acknowledgments

We thank Ms. K. Amann, PhD for her critical review; G. Weber, A. Kosel, and G. Herbig for their expert technical assistance; and M. Reid for proofreading the manuscript. This work was supported by a research grant from the University of Erlangen-Nuremberg (ELAN-Fond 98.08.14.1).

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Authors and Affiliations

  1. Institute of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany

    Sebastian Stintzing MD, Andreas Jung PhD, Thomas Kirchner MD & Daniel Neureiter MD

  2. Institute of Epidemiology and Social Medicine, University of Muenster, Muenster, Germany

    Peter Heuschmann MD

  3. Department of Vascular Surgery, University of Bochum, Bochum, Germany

    Letterio Barbera MD

  4. Department of Medicine I, University Erlangen-Nuernberg, Erlangen, Germany

    Sebastian Stintzing MD & Matthias Ocker MD

  5. Institute of Pathology, University of Erlangen-Nüremberg, Krankenhausstrasse 8–10, Erlangen, D-91054, Germany

    Daniel Neureiter MD

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  1. Sebastian Stintzing MD
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  2. Peter Heuschmann MD
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  4. Matthias Ocker MD
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Correspondence to Daniel Neureiter MD.

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Stintzing, S., Heuschmann, P., Barbera, L. et al. Overexpression of MMP9 and Tissue Factor in Unstable Carotid Plaques Associated with Chlamydia pneumoniae, Inflammation, and Apoptosis. Ann Vasc Surg 19, 310–319 (2005). https://doi.org/10.1007/s10016-005-0003-7

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  • DOI: https://doi.org/10.1007/s10016-005-0003-7

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