The Journal of Thoracic and Cardiovascular Surgery
Volume 138, Issue 3 , Pages 725-732, September 2009

Deleted in Malignant Brain Tumors 1 is up-regulated in bacterial endocarditis and binds to components of vegetations

  • Hanna Müller, MD

      Affiliations

    • Division of Neonatology, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany
    • Institute for Vascular Signalling, Centre of Molecular Medicine, Goethe University, Frankfurt/Main, Germany
    • Corresponding Author InformationAddress for reprints: Hanna Müller, MD, Institute for Vascular Signalling, Centre of Molecular Medicine, Goethe University, Theodor Stern Kai 7, 60590 Frankfurt/Main, Germany.
    • ,
  • Marcus Renner, PhD

      Affiliations

    • Division of Molecular Genome Analysis, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    • ,
  • Burkhard M. Helmke, MD

      Affiliations

    • Institute of Pathology, University of Heidelberg, Heidelberg, Germany
    • ,
  • Caroline End, PhD

      Affiliations

    • Division of Molecular Genome Analysis, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    • ,
  • Christel Weiss, PhD

      Affiliations

    • Institute of Medical Statistics and Biomathematics, University Hospital Mannheim, Mannheim, Germany
    • ,
  • Johannes Poeschl, MD

      Affiliations

    • Division of Neonatology, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany
    • ,
  • Jan Mollenhauer, PhD

      Affiliations

    • Division of Molecular Genome Analysis, Deutsches Krebsforschungszentrum, Heidelberg, Germany
    • Molecular Oncology, Medical Biotechnology Center, University of Southern Denmark, Odense, Denmark

Received 9 January 2009; received in revised form 19 April 2009; accepted 20 May 2009. published online 02 July 2009.

Objective

Bacterial endocarditis is a frequent infectious cardiac disease, especially in patients with congenital or acquired heart defects. It is characterized by bacterial colonization of the heart valves and the appearance of vegetations consisting of fibrin, blood cells, and bacteria. The glycoprotein Deleted in Malignant Brain Tumors 1 is a scavenger receptor cysteine-rich protein with functions in innate immunity and epithelial differentiation. Because of the aggregating capacity of Deleted in Malignant Brain Tumors 1, we hypothesized that an up-regulation in bacterial endocarditis may be linked to the development of vegetations.

Methods

Heart tissue of 19 patients with bacterial endocarditis and 10 controls without bacterial endocarditis was analyzed by immunohistochemistry. The effect of human recombinant Deleted in Malignant Brain Tumors 1 on erythrocyte aggregation was measured using an automated red blood cell aggregometer MA1. Binding of human recombinant Deleted in Malignant Brain Tumors 1 to erythrocyte membranes, platelets, fibrin, and fibrinogen was analyzed by Western blotting and enzyme-linked immunosorbent assay.

Results

Deleted in Malignant Brain Tumors 1 expression was up-regulated in affected heart valves with bacterial endocarditis and limited to the colonizing bacteria on the heart valves and granulocyte-depleted fibrin/fibrinogen formations, and around localized atheromatosis. Patients with aggressive bacteria showed higher DMBT1 levels than patients with less aggressive bacteria. Human recombinant Deleted in Malignant Brain Tumors 1 aggregates erythrocytes and binds to erythrocyte membranes, platelets, and fibrin/fibrinogen.

Conclusion

Deleted in Malignant Brain Tumors 1 up-regulation at sites of bacterial endocarditis, its association with platelets and fibrin/fibrinogen, and its ability to aggregate erythrocytes through binding to their membranes indicate a potential role in the development of vegetations and thrombosis.

Abbreviations and Acronyms: ACD, acidic citrate dextrose, DMBT1, Deleted in Malignant Brain Tumors 1, hr, human recombinant, HRP, horseradish peroxidase, Ig, immunoglobulin, PBS, phosphate-buffered saline

CTSNet classification: 17, 29, 35

To access this article, please choose from the options below

Login to an existing account or Register a new account.

  • Purchase this article for 31.50 USD (You must login/register to purchase this article)

    Online access for 24 hours. The PDF version can be downloaded as your permanent record.

  • Subscribe to this title

    Get unlimited online access to this article and all other articles in this title 24/7 for one year.

  • Claim access now

    For current subscribers with Society Membership or Account Number.

  • Visit SciVerse ScienceDirect to see if you have access via your institution.
 

 J. Poeschl and J. Mollenhauer contributed equally and should both be considered as senior authors.

 The work was supported by the BMBF Functional Nutritional Research Program grant no. FKZ 0313845 (to J.M.), and the BMBF Program Research Networks for Susceptibility and Resistance to Infection: PROGRESS-consortium grant no. FKZ 01KI07115 (to J.M.).

PII: S0022-5223(09)00761-2

doi:10.1016/j.jtcvs.2009.05.021

The Journal of Thoracic and Cardiovascular Surgery
Volume 138, Issue 3 , Pages 725-732, September 2009

Article Tools

* Image Usage & Resolution