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Right ventricular expression of extracellular matrix proteins, matrix-metalloproteinases, and their inhibitors over a period of 3 years after heart transplantation

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Abstract

Fibrillar collagens I and III, nonfibrillar collagen IV, and the glycoproteins fibronectin and laminin, are elements of the myocardial extracellular matrix (ECM). Alterations in the normal concentrations and ratios of these elements may reflect remodeling in response to physiologic stress. In the case of patients' post-heart transplantation (HTx), specific patterns of alteration may herald myocardial dysfunction. Right ventricular biopsies were taken from the same 28 HTx patients before implantation and 1 week, 2 weeks, and 1, 2, and 3 years after HTx. The above-noted five ECM proteins, six matrix metalloproteinases (MMPs) and two of their tissue inhibitors (TIMPs) were detected by immunohistochemistry and scored as cells per square millimeter or semiquantitatively. The total connective tissue fibers were detected by connective tissue stain and morphometry. Variations in these ECM components were followed in the same patient cohort over 3 years. In summary, during the first 2 weeks after HTx, a predominant increase in connective tissue occurred. Increases in MMP-8 and MMP-9 were found. By 3 years after transplantation, there was a decrease of connective tissue fibers and a significant reduction of all ECM components and an increase in MMPs and TIMPs. These findings may reflect a pattern of remodeling specific to the transplanted heart.

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Acknowledgements

The authors thank Ms. G. Gorsberg for her excellent technical assistance, Ms. U. Horr for her help with the preparation of the photographs, and Dr. P.J. Dahlheimer for his assistance with computer issues. Funding: Forschungsfoerderungs-programm der medizinischen fakultaet Heidelberg, projektnr. 150/2001

To the best of our knowledge, this study, at the time of its execution, was performed in compliance with the laws of Germany.

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Authors and Affiliations

  1. Department of Pathology, University of Heidelberg, INF 220/221, 69120, Heidelberg, Germany

    D. J. Schupp, B. P. Huck, J. Sykora, C. Flechtenmacher, H. F. Otto & P. A. Schnabel

  2. Department of Pediatric Cardiology, University of Heidelberg, Heidelberg, Germany

    M. Gorenflo & H. E. Ulmer

  3. Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany

    A. Koch, F.-U. Sack & S. Hagl

  4. Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany

    M. Haass & H. A. Katus

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  1. D. J. Schupp
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Correspondence to P. A. Schnabel.

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Schupp, D.J., Huck, B.P., Sykora, J. et al. Right ventricular expression of extracellular matrix proteins, matrix-metalloproteinases, and their inhibitors over a period of 3 years after heart transplantation. Virchows Arch 448, 184–194 (2006). https://doi.org/10.1007/s00428-005-0050-z

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  • DOI: https://doi.org/10.1007/s00428-005-0050-z

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