Cell and Tissue Research

, Volume 337, Issue 1, pp 63–77 | Cite as

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

  • Mareike Barth
  • Heiderose Schumacher
  • Caecilia Kuhn
  • Payam Akhyari
  • Artur Lichtenberg
  • Werner W. FrankeEmail author
Regular Article


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.


Heart valves Interstitial cells Adherens junctions Cadherins Plakophilin-2 Human Cow Sheep 



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

Supplementary material

441_2009_806_MOESM1_ESM.doc (34 kb)
ESM 1 (DOC 34 kb)


  1. Abdelwahid E, Pelliniemi LJ, Jokinen E (2002) Cell death and differentiation in the development of the endocardial cushion of the embryonic heart. Microsc Res Tech 58:395–403PubMedCrossRefGoogle Scholar
  2. Agarwal SK, Lee DM, Kiener HP, Brenner MB (2008) Coexpression of two mesenchymal cadherins, cadherin 11 and N-cadherin, on murine fibroblast-like synoviocytes. Arthritis Rheum 58:1044–1054PubMedCrossRefGoogle Scholar
  3. Anastasiadis PZ, Reynolds AB (2000) The p120 catenin family: complex roles in adhesion, signaling and cancer. J Cell Sci 113:1319–1334PubMedGoogle Scholar
  4. Aranishi H, Kunisawa Y, Komuro T (2009) Characterization of interstitial cells of Cajal in the subserosal layer of the guinea-pig colon. Cell Tissue Res 335:323–329PubMedCrossRefGoogle Scholar
  5. Armstrong EJ, Bischoff J (2004) Heart valve development. Endothelial cell signaling and differentiation. Circ Res 95:459–470PubMedCrossRefGoogle Scholar
  6. Bairati A, DeBiasi S (1981) Presence of a smooth muscle system in aortic valve leaflets. Anat Embryol (Berl) 161:329–340CrossRefGoogle Scholar
  7. Bertipaglia B, Ortolani F, Petrelli L, Gerosa G, Spina M, Pauletto P, Casarotto D, Marchini M, Sartore S (2003) Vitalitate exornatum succedaneum aorticum labore ingenioso obtenibitur project. Cell characterization of porcine aortic valve and decellularized leaflets repopulated with aortic valve interstitial cells: the VESALIO Project (Vitalitate Exornatum Succedaneum Aorticum Labore Ingenioso Obtenibitur). Ann Thorac Surg 75:1274–1282PubMedCrossRefGoogle Scholar
  8. Bierkamp C, McLaughlin KJ, Schwarz H, Huber O, Kemler R (1996) Embryonic heart and skin defects in mice lacking plakoglobin. Dev Biol 180:780–785PubMedCrossRefGoogle Scholar
  9. Blevins TL, Carroll JL, Raza AM, Grande-Allen KJ (2006) Phenotypic characterization of isolated valvular interstitial cell subpopulations. J Heart Valve Dis 15:815–822PubMedGoogle Scholar
  10. Boda-Heggemann J, Régnier-Vigouroux A, Franke WW (2009) Beyond vessels: occurrence and regional clustering of vascular endothelial (VE-) cadherin-containing junctions in non-endothelial cells. Cell Tissue Res 335:49–65PubMedCrossRefGoogle Scholar
  11. Borrmann CM, Grund C, Kuhn C, Hofmann I, Pieperhoff S, Franke WW (2006) The area composita of adhering junctions connecting heart muscle cells of vertebrates. II. Colocalizations of desmosomal and fascia adhaerens molecules in the intercalated disk. Eur J Cell Biol 85:469–485PubMedCrossRefGoogle Scholar
  12. Brand NJ, Roy A, Hoare G, Chester A, Yacoub MH (2006) Cultured interstitial cells from human heart valves express both specific skeletal muscle and non-muscle markers. Int J Biochem Cell Biol 38:30–42PubMedCrossRefGoogle Scholar
  13. Calkins H (2006) Arrhythmogenic right-ventricular dysplasia/cardiomyopathy. Curr Opin Cardiol 21:55–63PubMedCrossRefGoogle Scholar
  14. Canty EG, Kadler KE (2005) Procollagen trafficking, processing and fibrillogenesis. J Cell Sci 118:1341–1353PubMedCrossRefGoogle Scholar
  15. Canty EG, Lu Y, Meadows RS, Shaw MK, Holmes DF, Kadler KE (2004) Coalignment of plasma membrane channels and protrusions (fibripositors) specifies the parallelism of tendon. J Cell Biol 165:553–563PubMedCrossRefGoogle Scholar
  16. Cebotari S, Lichtenberg A, Tudorache I, Hilfiker A, Mertsching H, Leyh R, Breymann T, Kallenbach K, Maniuc L, Batrinac A, Repin O, Maliga O, Ciubotaru A, Haverich A (2006) Clinical application of tissue engineered human heart valves using autologous progenitor cells. Circulation 114:I132–I137PubMedCrossRefGoogle Scholar
  17. Chen X, Bonné S, Hatzfeld M, Roy F van, Green KJ (2002) Protein binding and functional characterization of plakophilin 2. J Biol Chem 277:10512–10522PubMedCrossRefGoogle Scholar
  18. Chester AH, Taylor PM (2007) Molecular and functional characteristics of heart valve interstitial cells. Phil Trans R Soc B 362:1437–1443PubMedCrossRefGoogle Scholar
  19. Cimini M, Rogers KA, Boughner DR (2003) Smoothelin-positive cells in human and porcine semilunar valves. Histochem Cell Biol 120:307–317PubMedCrossRefGoogle Scholar
  20. Compton CC, Raviola E (1985) Structure of the sinus-lining cells in the popliteal lymph node of the rabbit. Anat Rec 212:408–423PubMedCrossRefGoogle Scholar
  21. Filip DA, Radu A, Simionescu M (1986) Interstitial cells of the heart valves possess characteristics similar to smooth muscle cells. Circ Res 59:310–320PubMedGoogle Scholar
  22. Franke WW, Schmid E, Winter S, Osborn M, Weber K (1979a) Widespread occurrence of intermediate-sized filaments of the vimentin-type in cultured cells from diverse vertebrates. Exp Cell Res 123:25–46PubMedCrossRefGoogle Scholar
  23. Franke WW, Schmid E, Osborn M, Weber K (1979b) Intermediate-sized filaments of human endothelial cells. J Cell Biol 81:570–580PubMedCrossRefGoogle Scholar
  24. Franke WW, Schmid E, Vandekerckhove J, Weber K (1980) A permanently proliferating rat vascular smooth muscle cell with maintained expression of smooth muscle characteristics, including actin of the vascular smooth muscle type. J Cell Biol 87:594–600PubMedCrossRefGoogle Scholar
  25. Franke WW, Borrmann CM, Grund C, Pieperhoff S (2006) The area composita of adhering junctions connecting heart muscle cells of vertebrates. I. Molecular definition in intercalated disks of cardiomyocytes by immunoelectron microscopy of desmosomal proteins. Eur J Cell Biol 85:69–82PubMedCrossRefGoogle Scholar
  26. Garg V, Muth AN, Ransom JF, Schluterman MK, Barnes R, King IN, Grossfeld PD, Srivastava D (2005) Mutations in NOTCH1 cause aortic valve disease. Nature 437:270–274PubMedCrossRefGoogle Scholar
  27. Gerull B, Heuser A, Wichter T, Paul M, Basson CT, McDermott DA, Lerman BB, Markowitz SM, Ellinor PT, MacRae C, Peters S, Grossmann KS, Drenckhahn J, Michely B, Sasse-Klaassen S, Birchmeier W, Dietz R, Breithardt G, Schulze-Bahr E, Thierfelder L (2004) Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy. Nat Genet 36:1162–1164PubMedCrossRefGoogle Scholar
  28. Gherghiceanu M, Popescu LM (2005) Interstitial Cajal-like cells (ICLC) in human resting mammary gland stroma. J Cell Mol Med 9:893–910PubMedCrossRefGoogle Scholar
  29. Gitler AD, Lu MM, Jiang YQ, Epstein JA, Gruber PJ (2003) Molecular markers of cardiac endocardial cushion development. Dev Dyn 228:643–650PubMedCrossRefGoogle Scholar
  30. Goodson HV, Hawse WF (2002) Molecular evolution of the actin family. J Cell Sci 115:2619–2622PubMedGoogle Scholar
  31. Goossens S, Janssens B, Bonné S, De Rycke R, Braet F, Hengel J van, Roy F van (2007) A unique and specific interaction between alphaT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs. J Cell Sci 120:2126–2136PubMedCrossRefGoogle Scholar
  32. Grossmann KS, Grund C, Huelsken J, Behrend M, Erdmann B, Franke WW, Birchmeier W (2004) Requirement of plakophilin 2 for heart morphogenesis and cardiac junction formation. J Cell Biol 167:149–160PubMedCrossRefGoogle Scholar
  33. Hatzfeld M (2005) The p120 family of cell adhesion molecules. Eur J Cell Biol 84:205–214PubMedCrossRefGoogle Scholar
  34. Hatzfeld M, Nachtsheim C (1996) Cloning and characterization of a new armadillo family member, p0071, associated with the junctional plaque: evidence for a subfamily of closely related proteins. J Cell Sci 109:2767–2778PubMedGoogle Scholar
  35. Heaysman JE, Pegrum SM (1973) Early contacts between fibroblasts. An ultrastructural study. Exp Cell Res 78:71–78PubMedCrossRefGoogle Scholar
  36. Herrmann H, Bär H, Kreplak L, Strelkov SV, Aebi U (2007) Intermediate filaments: from cell architecture to nanomechanics. Nat Rev Mol Cell Biol 8:562–573PubMedCrossRefGoogle Scholar
  37. Hinescu ME, Popescu LM (2005) Interstitial Cajal-like cells (ICLC) in human atrial myocardium. J Cell Mol Med 9:972–975PubMedCrossRefGoogle Scholar
  38. Hinescu ME, Gherghiceanu M, Mandache E, Ciontea SM, Popescu LM (2006) Interstitial Cajal-like cells (ICLC) in atrial myocardium: ultrastructural and immunohistochemical characterization. J Cell Mol Med 10:243–257PubMedCrossRefGoogle Scholar
  39. Hinz B, Pittet P, Smith-Clerc J, Chaponnier C, Meister J-J (2004) Myofibroblast development is characterized by specific cell-cell adherens junctions. Mol Biol Cell 15:4310–4320PubMedCrossRefGoogle Scholar
  40. Ho AD, Wagner W, Franke W (2008) Heterogeneity of mesenchymal stroma cell preparations. Cytotherapy 10:320–330PubMedCrossRefGoogle Scholar
  41. Hofmann I, Kuhn C, Franke WW (2008) Protein p0071, a major plaque protein of non-desmosomal adhering junctions, is a selective cell-type marker. Cell Tissue Res 334:381–399PubMedCrossRefGoogle Scholar
  42. Hofmann I, Schlechter T, Kuhn C, Hergt M, Franke WW (2009) Protein p0071—an armadillo plaque protein that characterizes a specific subtype of adherens junctions. J Cell Sci 122:21–24PubMedCrossRefGoogle Scholar
  43. Icardo JM, Colvee E (1995) Atrioventricular valves of the mouse. II. Light and transmission electron microscopy. Anat Rec 241:391–400PubMedCrossRefGoogle Scholar
  44. Kawaguchi J, Azuma Y, Hoshi K, Kii I, Takeshita S, Ohta T, Ozawa H, Takeichi M, Chisaka O, Kudo A (2001a) Targeted disruption of cadherin-11 leads to a reduction in bone density in calvaria and long bone metaphyses. J Bone Miner Res 16:1265–1271PubMedCrossRefGoogle Scholar
  45. Kawaguchi J, Kii I, Sugiyama Y, Takeshita S, Kudo A (2001b) The transition of cadherin expression in osteoblast differentiation from mesenchymal cells: consistent expression of cadherin-11 in osteoblast lineage. J Bone Miner Res 16:260–269PubMedCrossRefGoogle Scholar
  46. Kiener HP, Brenner MB (2005) Building the synovium: cadherin-11 mediates fibroblast-like synoviocyte cell-to-cell adhesion. Arthritis Res Ther 7:49–54PubMedCrossRefGoogle Scholar
  47. Kimura Y, Matsunami H, Inoue T, Shimamura K, Uchida N, Ueno T, Miyazaki T, Takeichi M (1995) Cadherin-11 expressed in association with mesenchymal morphogenesis in the head, somite, and limb bud of early mouse embryos. Dev Biol 169:347–358PubMedCrossRefGoogle Scholar
  48. Kinner B, Zaleskas JM, Spector M (2002) Regulation of smooth muscle actin expression and contraction in adult human mesenchymal stem cells. Exp Cell Res 278:72–83PubMedCrossRefGoogle Scholar
  49. Knapp AC, Franke WW (1989) Spontaneous losses of control of cytokeratin gene expression in transformed, non-epithelial human cells occurring at different levels of regulation. Cell 59:67–79PubMedCrossRefGoogle Scholar
  50. Knapp AC, Bosch FX, Hergt M, Kuhn C, Winter-Simanowski S, Schmid E, Regauer S, Bartek J, Franke WW (1989) Cytokeratins and cytokeratin filaments in subpopulations of cultured human and rodent cells of nonepithelial origin: modes and patterns of formation. Differentiation 42:81–102PubMedCrossRefGoogle Scholar
  51. Koeser J, Troyanovsky SM, Grund C, Franke WW (2003) De novo formation of desmosomes in cultured cells upon transfection of genes encoding specific desmosomal components. Exp Cell Res 285:114–130PubMedCrossRefGoogle Scholar
  52. Kostetskii I, Li J, Xiong Y, Zhou R, Ferrari VA, Patel VV, Molkentin JD, Radice GL (2005) Induced deletion of the N-cadherin gene in the heart leads to dissolution of the intercalated disc structure. Circ Res 96:346–354PubMedCrossRefGoogle Scholar
  53. Kühnel W (1966a) Elektronenmikroskopische Untersuchungen über den unterschiedlichen Bau der Herzklappen. I. Mitteilung Mitralis und Aortenklappe. Z Zellforsch 69:452–473PubMedCrossRefGoogle Scholar
  54. Kühnel W (1966b) Elektronenmikroskopische Untersuchungen über den unterschiedlichen Bau der Herzklappen. II. Mitteilung Tricuspidalis und Pulmonalklappe. Z Zellforsch 72:462–474PubMedCrossRefGoogle Scholar
  55. Langbein L, Rogers MA, Praetzel S, Aoki N, Winter H, Schweizer J (2002) A novel epithelial keratin, hK6irs1, is expressed differentially in all layers of the inner root sheath, including specialized huxley cells (Flügelzellen) of the human hair follicle. J Invest Dermatol 118:789–799PubMedCrossRefGoogle Scholar
  56. Lange FJ de, Moorman AFM, Anderson RH, Männer J, Soufan AT, Gier-de Vries C de, Schneider MD, Webb S, Hoff MJB van den, Christoffels VM (2004) Lineage and morphogenetic analysis of the cardiac valves. Circ Res 95:645–654PubMedCrossRefGoogle Scholar
  57. Latif N, Sarathchandra P, Taylor PM, Antoniw J, Yacoub MH (2005a) Localization and pattern of expression of extracellular matrix components in human heart valves. J Heart Valve Dis 14:218–227PubMedGoogle Scholar
  58. Latif N, Sarathchandra P, Taylor PM, Antoniw J, Yacoub MH (2005b) Molecules mediating cell-ECM and cell-cell communication in human heart valves. Cell Biochem Biophys 43:275–287PubMedCrossRefGoogle Scholar
  59. Latif N, Sarathchandra P, Taylor PM, Antoniw J, Brand N, Yacoub MH (2006) Characterization of molecules mediating cell-cell communication in human cardiac valve interstitial cells. Cell Biochem Biophys 45:255–264PubMedCrossRefGoogle Scholar
  60. Latif N, Sarathchandra P, Thomas PS, Antoniw J, Batten P, Chester AH, Taylor PM, Yacoub MH (2007) Characterization of structural and signaling molecules by human valve interstitial cells and comparison to human mesenchymal stem cells. J Heart Valve Dis 16:56–66PubMedGoogle Scholar
  61. Lichtenberg A, Tudorache I, Cebotari S, Suprunov M, Tudorache G, Goerler H, Park JK, Hilfiker-Kleiner D, Ringes-Lichtenberg S, Karck M, Brandes G, Hilfiker A, Haverich A (2006) Preclinical testing of tissue-engineered heart valves re-endothelialized under simulated physiological conditions. Circulation 114:I559–I565PubMedCrossRefGoogle Scholar
  62. Liu AC, Gotlieb AI (2007) Characterization of cell motility in single heart valve interstitial cells in vitro. Histol Histopathol 22:873–882PubMedGoogle Scholar
  63. Lester W, Rosenthal A, Granton B, Gotlieb AI (1988) Porcine mitral valve interstitial cells in culture. Lab Invest 59:710–719PubMedGoogle Scholar
  64. Lester WM, Damji AA, Tanaka M, Gedeon I (1992) Bovine mitral valve organ culture: role of interstitial cells in repair of valvular injury. J Mol Cell Cardiol 24:43–53PubMedCrossRefGoogle Scholar
  65. Marcus FI, Nava A, Thiene G (2007) Arrhythmogenic right ventricular cardiomyopathy/dysplasia. Springer, Berlin CrossRefGoogle Scholar
  66. McHugh KM, Crawford K, Lessard J (1991) A comprehensive analysis of the developmental and tissue-specific expression of the isoactin multigene family in the rat. Dev Biol 148:442–458PubMedCrossRefGoogle Scholar
  67. Mertens C, Kuhn C, Franke WW (1996) Plakophilins 2a and 2b: constitutive proteins of dual location in the karyoplasm and the desmosomal plaque. J Cell Biol 135:1009–1025PubMedCrossRefGoogle Scholar
  68. Mertens C, Hofmann I, Wang Z, Teichmann M, Sepehri Chong S, Schnölzer M, Franke WW (2001) Nuclear particles containing RNA polymerase III complexes associated with the junctional plaque protein plakophilin 2. Proc Natl Acad Sci USA 98:7795–7800PubMedCrossRefGoogle Scholar
  69. Messier RH Jr, Bass BL, Aly HM, Jones JL, Domkowski PW, Wallace RB, Hopkins RA (1994) Dual structural and functional phenotypes of the porcine aortic valve interstitial population: characteristics of the leaflet myofibroblast. J Surg Res 57:1–21PubMedCrossRefGoogle Scholar
  70. Moll R, Holzhausen HJ, Mennel HD, Kuhn C, Baumann R, Taege C, Franke WW (2006) The cardiac isoform of alpha-actin in regenerating and atrophic skeletal muscle, myopathies and rhabdomyomatous tumors: an immunohistochemical study using monoclonal antibodies. Virchows Arch 449:175–191PubMedCrossRefGoogle Scholar
  71. Moll R, Sievers E, Hämmerling B, Schmidt A, Barth M, Kuhn C, Grund C, Hofmann I, Franke WW (2009) Endothelial and virgultar cell formations in the mammalian lymph node sinus: endothelial differentiation morphotypes characterized by a special kind of junction (complexus adhaerens). Cell Tissue Res 335:109–141PubMedCrossRefGoogle Scholar
  72. Mulholland DL, Gotlieb AI (1996) Cell biology of valvular interstitial cells. Can J Cardiol 12:231–236PubMedGoogle Scholar
  73. Neuss M, Regitz-Zagrosek V, Hildebrandt A, Fleck E (1996) Isolation and characterisation of human cardiac fibroblasts from explanted adult hearts. Cell Tissue Res 286:145–153PubMedCrossRefGoogle Scholar
  74. Norris RA, Moreno-Rodriguez RA, Sugi Y, Hoffman S, Amos J, Hart MM, Potts JD, Goodwin RL, Markwald RR (2008) Periostin regulates atrioventricular valve maturation. Dev Biol 316:200–221PubMedCrossRefGoogle Scholar
  75. Paffenholz R, Franke WW (1997) Identification and localization of a neurally expressed member of the plakoglobin/armadillo multigene family. Differentiation 61:293–304PubMedCrossRefGoogle Scholar
  76. Paffenholz R, Kuhn C, Grund C, Stehr S, Franke WW (1999) The arm-repeat protein NPRAP (neurojungin) is a constituent of the plaques of the outer limiting zone in the retina, defining a novel type of adhering junction. Exp Cell Res 250:452–464PubMedCrossRefGoogle Scholar
  77. Person AD, Klewer S, Runyan RB (2005) Cell biology of cardiac cushion development. Int Rev Cytol 243:287–335PubMedCrossRefGoogle Scholar
  78. Pho M, Lee W, Watt DR, Laschinger C, Simmons CA, McCulloch CA (2008) Cofilin is a marker of myofibroblast differentiation in cells from porcine aortic cardiac valves. Am J Physiol Heart Circ Physiol 294:H1767–H1778PubMedCrossRefGoogle Scholar
  79. Pieperhoff S, Franke WW (2007) The area composita of adhering junctions connecting heart muscle cells of vertebrates. IV. Coalescence and amalgamation of desmosomal and adhaerens junction components—late processes in mammalian heart development. Eur J Cell Biol 86:377–391PubMedCrossRefGoogle Scholar
  80. Pieperhoff S, Franke WW (2008) The area composita of adhering junctions connecting heart muscle cells of vertebrates. VI. Different precursor structures in non-mammalian species. Eur J Cell Biol 87:413–430PubMedCrossRefGoogle Scholar
  81. Pieperhoff S, Schumacher H, Franke WW (2008) The area composita of adhering junctions connecting heart muscle cells of vertebrates. V. The importance of plakophilin-2 demonstrated by small interference RNA-mediated knockdown in cultured rat cardiomyocytes. Eur J Cell Biol 87:399–411PubMedCrossRefGoogle Scholar
  82. Pittet P, Lee K, Kulik AJ, Meister JJ, Hinz B (2008) Fibrogenic fibroblasts increase intercellular adhesion strength by reinforcing individual OB-cadherin bonds. J Cell Sci 121:877–886PubMedCrossRefGoogle Scholar
  83. Ploetz C, Zycband EI, Birk DE (1991) Collagen fibril assembly and deposition in the developing dermis: segmental deposition in extracellular compartments. J Struct Biol 106:73–81PubMedCrossRefGoogle Scholar
  84. Popescu LM, Hinescu ME, Ionescu N, Ciontea SM, Cretoiu D, Ardeleanu C (2005) Interstitial cells of Cajal in pancreas. J Cell Mol Med 9:169–190PubMedCrossRefGoogle Scholar
  85. Popescu LM, Gherghiceanu M, Hinescu ME, Cretoiu D, Ceafalan L, Regalia T, Popescu AC, Ardeleanu C, Mandache E (2006) Insights into the interstitium of ventricular myocardium: interstitial Cajal-like cells (ICLC). J Cell Mol Med 10:429–458PubMedCrossRefGoogle Scholar
  86. Richardson SH, Starborg T, Lu Y, Humphries SM, Meadows RS, Kadler KE (2007) Tendon development requires regulation of cell condensation and cell shape via cadherin-11 mediated cell-cell junctions. Mol Cell Biol 27:6218–6228PubMedCrossRefGoogle Scholar
  87. Rickelt S, Franke WW, Doerflinger Y, Goerdt S, Brandner JM, Peitsch WK (2008) Subtypes of melanocytes and melanoma cells distinguished by their intercellular contacts: heterotypic adherens junctions, adhesive associations, and dispersed desmoglein 2 glycoproteins. Cell Tissue Res 334:401–422PubMedCrossRefGoogle Scholar
  88. Ruiz P, Brinkmann V, Ledermann B, Behrend M, Grund C, Thalhammer C, Vogel F, Birchmeier C, Günthert U, Franke WW, Birchmeier W (1996) Targeted mutation of plakoglobin in mice reveals essential functions of desmosomes in the embryonic heart. J Cell Biol 135:215–225PubMedCrossRefGoogle Scholar
  89. Schenke-Leyland K, Riemann I, Opitz F, König K, Halbhuber KJ, Stock UA (2004) Comparative study of cellular and extracellular matrix composition of native and tissue engineered heart valves. Matrix Biol 23:113–125CrossRefGoogle Scholar
  90. Schmitt CJ, Franke WW, Goerdt S, Falkowska-Hansen B, Rickelt S, Peitsch WK (2007) Homo- and heterotypic cell contacts in malignant melanoma cells and desmoglein 2 as a novel solitary surface glyocprotein. J Invest Dermatol 127:2191–2206PubMedCrossRefGoogle Scholar
  91. Schoen FJ (2008) Evolving concepts of cardiac valve dynamics: the continuum of development, functional structure, pathobiology, and tissue engineering. Circulation 118:1864–1880PubMedCrossRefGoogle Scholar
  92. Shelton EL, Yutzey KE (2008) Twist1 function in endocardial cushion cell proliferation, migration, and differentiation during heart valve development. Dev Biol 317:282–295PubMedCrossRefGoogle Scholar
  93. Shi SR, Key ME, Kalra KL (1991) Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem 39:741–748PubMedGoogle Scholar
  94. Simonneau L, Kitagawa M, Suzuki S, Thiery JP (1995) Cadherin 11 expression marks the mesenchymal phenotype: towards new functions for cadherins? Cell Adhes Commun 3:115–30PubMedCrossRefGoogle Scholar
  95. Sirotkin H, O’Donnell H, DasGupta R, Halford S, St Jore B, Puech A, Parimoo S, Morrow B, Skoultchi A, Weissman SM, Scambler P, Kucherlapati R (1997) Identification of a new human catenin gene family member (ARVCF) from the region deleted in velo-cardio-facial syndrome. Genomics 41:75–83PubMedCrossRefGoogle Scholar
  96. Srivastava D (2005) Making or breaking the heart: from lineage determination to morphogenesis. Cell 126:1037–1048CrossRefGoogle Scholar
  97. Taylor PM, Allen SP, Yacoub MH (2000) Phenotypic and functional characterization of interstitial cells from human heart valves, pericardium and skin. J Heart Valve Dis 9:150–158PubMedGoogle Scholar
  98. Taylor PM, Batten P, Brand NJ, Thomas PS, Yacoub MH (2003) The cardiac valve interstitial cell. Int J Biochem Cell Biol 35:113–118PubMedCrossRefGoogle Scholar
  99. Valencia X, Higgins JM, Kiener HP, Lee DM, Podrebarac TA, Dascher CC, Watts GF, Mizoguchi E, Simmons B, Patel DD, Bhan AK, Brenner MB (2004) Cadherin-11 provides specific cellular adhesion between fibroblast-like synoviocytes. J Exp Med 200:1673–1679PubMedCrossRefGoogle Scholar
  100. Vandekerckhove J, Weber K (1979) The complete amino acid sequence of actins from bovine aorta, bovine heart, bovine fast skeletal muscle, and rabbit slow skeletal muscle. A protein-chemical analysis of muscle actin differentiation. Differentiation 14:123–133PubMedCrossRefGoogle Scholar
  101. Visconti RP, Ebihara Y, LaRue AC, Fleming PA, McQuinn TC, Masuya M, Minamiguchi H, Markwald RR, Ogawa M, Drake CJ (2006) An in vivo analysis of hematopoietic stem cell potential: hematopoietic origin of cardiac valve interstitial cells. Circ Res 98:690–696PubMedCrossRefGoogle Scholar
  102. Walker GY, Masters KS, Shah DN, Anseth KS, Leinwand LA (2004) Valvular myofibroblast activation by transforming growth factor-β: implications for pathological extracellular matrix remodeling in heart valve disease. Circ Res 95:253–260PubMedCrossRefGoogle Scholar
  103. Walter B, Schlechter T, Hergt M, Berger I, Hofmann I (2008) Differential expression pattern of protein ARVCF in nephron segments of human and mouse kidney. Histochem Cell Biol 130:943–956PubMedCrossRefGoogle Scholar
  104. Wheelock MJ, Shintani Y, Maeda M, Fukumoto Y, Johnson KR (2008) Cadherin switching. J Cell Sci 121:727–735PubMedCrossRefGoogle Scholar
  105. Wuchter P, Boda-Heggemann J, Straub BK, Grund C, Kuhn C, Krause U, Seckinger A, Peitsch WK, Spring H, Ho AD, Franke WW (2007) Processus and recessus adhaerentes: giant adherens cell junction systems connect and attract human mesenchymal stem cells. Cell Tissue Res 328:499–514PubMedCrossRefGoogle Scholar
  106. Yang GC, Birk DE (1986) Topographies of extracytoplasmic compartments in developing chick tendon fibroblasts. J Ultrastruct Mol Struct Res 97:238–248PubMedCrossRefGoogle Scholar
  107. Yperman J, De Visscher G, Holvoet P, Flameng W (2004) Molecular and functional characterization of ovine cardiac valve-derived interstitial cells in primary isolates and cultures. Tissue Eng 10:1368–1375PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Mareike Barth
    • 1
  • Heiderose Schumacher
    • 1
  • Caecilia Kuhn
    • 1
  • Payam Akhyari
    • 2
    • 3
  • Artur Lichtenberg
    • 2
    • 3
  • Werner W. Franke
    • 1
    Email author
  1. 1.Helmholtz Group/Cell BiologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  2. 2.Department of Cardiac SurgeryUniversity of Heidelberg Medical SchoolHeidelbergGermany
  3. 3.Department of Cardiothoracic SurgeryUniversity Hospital JenaJenaGermany

Personalised recommendations