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Changes in extra cellular matrix remodelling and re-expression of fibronectin and tenascin-C splicing variants in human myocardial tissue of the right atrial auricle: implications for a targeted therapy of cardiovascular diseases using human SIP format antibodies

Journal of Molecular Histology volume 41, pages 39–50 (2010)Cite this article

Abstract

Cardiovascular diseases are accompanied by changes in the extracellular matrix (ECM) including the re-expression of fibronectin and tenascin-C splicing variants. Using human recombinant small immunoprotein (SIP) format antibodies, a molecular targeting of these proteins is of therapeutic interest. Tissue samples of the right atrial auricle from patients with coronary artery disease and valvular heart disease were analysed by PCR based ECM gene expression profiling. Moreover, the re-expression of fibronectin and tenascin-C splicing variants was investigated by immunofluoerescence labelling. We demonstrated changes in ECM gene expression depending on histological damage or underlying cardiac disease. An increased expression of fibronectin and tenascin-C mRNA in association to histological damage and in valvular heart disease compared to coronary artery disease could be shown. There was a distinct re-expression of ED-A containing fibronectin and A1 domain containing tenascin-C detectable with human recombinant SIP format antibodies in diseased myocardium. ED-A containing fibronectin showed a clear vessel positivity. For A1 domain containing tenascin-C, there was a particular positivity in areas of interstitial and perivascular fibrosis. Right atrial myocardial tissue is a valuable model to investigate cardiac ECM remodelling. Human recombinant SIP format antibodies usable for an antibody-mediated targeted delivery of drugs might offer completely new therapeutic options in cardiac diseases.

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Acknowledgments

The authors are grateful to Professor Ismo Virtanen for providing the anti-laminin α4 chain antibody FC10. Furthermore, the authors would like to thank Claudia Seliger and Katrin Hornung for excellent technical assistance. The research leading to the results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n° Health-F2-2008-201342 (ADAMANT).

Conflict of interest statement

Dario Neri is a co-founder and shareholder of Philogen, the company which owns the rights over the F8, L19, F16 and G11 antibodies.

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Affiliations

  1. Department of Internal Medicine I, University Hospital Jena, Erlanger Allee 101, 07740, Jena, Germany

    Marcus Franz, Bernhard R. Brehm & Hans R. Figulla

  2. Institute of Pathology, University Hospital Jena, Jena, Germany

    Petra Richter & Alexander Berndt

  3. Department of Cardiothoracic Surgery, University Hospital Jena, Jena, Germany

    Katja Gruen & Khosro Hekmat

  4. Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland

    Dario Neri

  5. Institute of Pathology, HELIOS-Klinikum Erfurt, Erfurt, Germany

    Hartwig Kosmehl

  6. Clinic for Thoracic and Cardiovascular Surgery, Heart Center North Rhine- Westphalia, Ruhr-University of Bochum, Bad Oeynhausen, Germany

    Andre Renner & Jan Gummert

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  1. Marcus Franz
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  2. Bernhard R. Brehm
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  3. Petra Richter
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  4. Katja Gruen
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  5. Dario Neri
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  8. Andre Renner
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  9. Jan Gummert
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  10. Hans R. Figulla
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  11. Alexander Berndt
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Corresponding author

Correspondence to Marcus Franz.

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Marcus Franz and Bernhard R. Brehm contributed equally to the study.

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Franz, M., Brehm, B.R., Richter, P. et al. Changes in extra cellular matrix remodelling and re-expression of fibronectin and tenascin-C splicing variants in human myocardial tissue of the right atrial auricle: implications for a targeted therapy of cardiovascular diseases using human SIP format antibodies. J Mol Hist 41, 39–50 (2010). https://doi.org/10.1007/s10735-010-9260-z

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  • DOI: https://doi.org/10.1007/s10735-010-9260-z

Keywords

  • Fibronectin
  • Tenascin-C
  • Coronary artery disease
  • Valvular heart disease
  • Targeted therapy