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Cordial connections: molecular ensembles and structures of adhering junctions connecting interstitial cells of cardiac valves in situ and in cell culture

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Abstract

Remarkable efforts have recently been made in the tissue engineering of heart valves to improve the results of valve transplantations and replacements, including the design of artificial valves. However, knowledge of the cell and molecular biology of valves and, specifically, of valvular interstitial cells (VICs) remains limited. Therefore, our aim has been to determine and localize the molecules forming the adhering junctions (AJs) that connect VICs in situ and in cell culture. Using biochemical and immunolocalization methods at the light- and electron-microscopic levels, we have identified, in man, cow, sheep and rat, the components of VIC-connecting AJs in situ and in cell culture. These AJs contain, in addition to the transmembrane glycoproteins N-cadherin and cadherin-11, the typical plaque proteins α- and β-catenin as well as plakoglobin and p120, together with minor amounts of protein p0071, i.e. a total of five plaque proteins of the armadillo family. While we can exclude the occurrence of desmogleins, desmocollins and desmoplakin, we have noted with surprise that AJs of VICs in cell cultures, but not those growing in the valve tissue, contain substantial amounts of the desmosomal plaque protein, plakophilin-2. Clusters of AJs occur not only on the main VIC cell bodies but are also found widely dispersed on their long filopodia thus forming, in the tissue, a meshwork that, together with filopodial attachments to paracrystalline collagen fiber bundles, establishes a three-dimensional suprastructure, the role of which is discussed with respect to valve formation, regeneration and function.

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Acknowledgments

The authors thank Christine Grund for expert technical consultations and Eva Gundel for careful composition of the typescript.

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Author notes

  1. Payam Akhyari & Artur Lichtenberg

    Present address: Department of Cardiothoracic Surgery, University Hospital Jena, Erlanger Allee 101, 07747, Jena, Germany

Authors and Affiliations

  1. Helmholtz Group/Cell Biology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany

    Mareike Barth, Heiderose Schumacher, Caecilia Kuhn & Werner W. Franke

  2. Department of Cardiac Surgery, University of Heidelberg Medical School, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany

    Payam Akhyari & Artur Lichtenberg

Authors
  1. Mareike Barth
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  2. Heiderose Schumacher
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  3. Caecilia Kuhn
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  4. Payam Akhyari
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  5. Artur Lichtenberg
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  6. Werner W. Franke
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Corresponding author

Correspondence to Werner W. Franke.

Additional information

The work was supported by grants from the Deutsche Krebshilfe (grant 10-2049-Fr1 to W.W.F.) and the German Ministry for Education and Research (BMBF) in a cooperative research program entitled “Standardization of mesenchymal stem cells for regenerative medicine (START-MSC)”.

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Barth, M., Schumacher, H., Kuhn, C. et al. Cordial connections: molecular ensembles and structures of adhering junctions connecting interstitial cells of cardiac valves in situ and in cell culture. Cell Tissue Res 337, 63–77 (2009). https://doi.org/10.1007/s00441-009-0806-x

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  • DOI: https://doi.org/10.1007/s00441-009-0806-x

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