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J Thorac Cardiovasc Surg 2009;138:725-732
© 2009 The American Association for Thoracic Surgery

Evolving Technology/Basic Science

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

^a Division of Neonatology, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany
^b Institute for Vascular Signalling, Centre of Molecular Medicine, Goethe University, Frankfurt/Main, Germany
^c Division of Molecular Genome Analysis, Deutsches Krebsforschungszentrum, Heidelberg, Germany
^d Institute of Pathology, University of Heidelberg, Heidelberg, Germany
^e Institute of Medical Statistics and Biomathematics, University Hospital Mannheim, Mannheim, Germany
^f Molecular Oncology, Medical Biotechnology Center, University of Southern Denmark, Odense, Denmark

Received for publication January 9, 2009; revisions received April 19, 2009; accepted for publication May 20, 2009.

^_* Address for reprints: Hanna Müller, MD, Institute for Vascular Signalling, Centre of Molecular Medicine, Goethe University, Theodor Stern Kai 7, 60590 Frankfurt/Main, Germany. (Email: Mueller{at}vrc.uni-frankfurt.de).

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.

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				H. Muller, J. Hu, R. Popp, M. H. H. Schmidt, K. Muller-Decker, J. Mollenhauer, B. Fisslthaler, J. A. Eble, and I. Fleming Deleted in Malignant Brain Tumors 1 is Present in the Vascular Extracellular Matrix and Promotes Angiogenesis Arterioscler Thromb Vasc Biol, February 1, 2012; 32(2): 442 - 448. [Abstract] [Full Text] [PDF]