Skip to main content

Cell Adhesion Pathology

  • Chapter

Abstract

Significant progress has been made in identifying single gene mutations responsible for causing human cardiomyopathies. Although many of these monogenic cardiomyopathies are rare, insights into pathogenesis by identification of the responsible mutations can provide clues about mechanisms in more common forms of heart disease.We have studied a group of human cardiomyopathies caused by mutations in genes encoding proteins that function as linkers in cell-cell adhesion junctions. These heart diseases, which we have termed cell-cell junction cardiomyopathies, are caused by mutations in intracellular proteins that link adhesion molecules at adherens junctions and desmosomes to the myocyte cytoskeleton. Among the genes implicated in these diseases are those encoding desmoplakin, plakoglobin, and plakophilin-2. These mutations have both dominant and recessive patterns of inheritance and are associated with clinical phenotypes of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) or dilat cardiomyopathy (DCM), with or without hair and skin abnormalities [1].Common features of the cell-cell junction cardiomyopathies are a high incidence of syncope, ventricular arrhythmias, and sudden cardiac death. This observation suggests that alterations in intercellular adhesion caused by defects in cell-cell mechanical junctions may create anatomic substrates that are particularly conducive to the development of lethal ventricular arrhythmias. Our work in this area has focused on the hypothesis that defective mechanical linkage in the cell-cell junction cardiomyopathies causes remodeling of gap junctions, which, in turn, can give rise to conduction abnormalities that may contribute to the high incidence of sudden death in these patients.

Keywords

  • Junction Protein
  • Intercalate Disk
  • Palmoplantar Keratoderma
  • Woolly Hair
  • Naxos Disease

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-88-470-0490-0_6
  • Chapter length: 7 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   189.00
Price excludes VAT (USA)
  • ISBN: 978-88-470-0490-0
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   249.99
Price excludes VAT (USA)
Hardcover Book
USD   249.99
Price excludes VAT (USA)

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Protonotarios N, Tsatsopoulou A (2004) Naxos disease and Carvajal syndrome: cardiocutaneous disorders that highlight the pathogenesis and broaden the spectrum of arrhythmogenic right ventricular cardiomyopathy. Cardiovasc Pathol 13:185–194

    PubMed  CrossRef  CAS  Google Scholar 

  2. Saffitz JE, Lerner DL, Yamada KA (2004) Gap junction distribution and regulation in the heart. In: Zipes DP, Jalife J, (eds) Cardiac electrophysiology: From cell to bedside, 4th edn. Saunders, Philadelphia pp 181–191

    Google Scholar 

  3. Saffitz JE (2005) Dependence of electrical coupling on mechanical coupling in cardiac myocytes: insights gained from cardiomyopathies caused by defects in cell-cell connections. Ann N Y Acad Sci 1047:336–344

    PubMed  CrossRef  CAS  Google Scholar 

  4. Kaplan SR, Gard JJ, Protonotarios N et al (2004) Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease). Heart Rhythm 1:3–11

    PubMed  CrossRef  Google Scholar 

  5. Protonotarios N, Tsatsopoulou AA, Gatzoulis KA (2002) Arrhythmogenic right ventricular cardiomyopathy caused by a deletion in plakoglobin (Naxos disease). Card Electrophysiol Rev 6:72–80

    PubMed  CrossRef  Google Scholar 

  6. Protonotarios N, Tsatsopoulou A, Anastasakis A et al (2001) Genotype-phenotype assessment in autosomal recessive arrhythmogenic right ventricular cardiomyopathy (Naxos disease) caused by a deletion in plakoglobin. J Am Coll Cardiol 38:1477–1484

    PubMed  CrossRef  CAS  Google Scholar 

  7. McKoy G, Protonotarios N, Crosby A et al (2000) Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease). Lancet 355:2119–2124

    PubMed  CrossRef  CAS  Google Scholar 

  8. Carvajal-Huerta L (1998) Epidermolytic palmoplantar keratoderma with woolly hair and dilated cardiomyopathy. J Am Acad Dermatol 39:418–421

    PubMed  CrossRef  CAS  Google Scholar 

  9. Norgett EE, Hatsell SJ, Carvajal-Huerta L et al (2000) Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma. Hum Mol Genet 9:2671–2766

    CrossRef  Google Scholar 

  10. Kaplan SR, Gard JJ, Carvajal-Huerta L et al (2004) Structural and molecular pathology of the heart in Carvajal syndrome. Cardiovasc Pathol 13:26–32

    PubMed  CrossRef  CAS  Google Scholar 

  11. Wang X, Osinska H, Dorn GW 2nd et al (2001) Mouse model of desmin-related cardiomyopathy. Circulation 103:2402–2407

    PubMed  CAS  Google Scholar 

  12. Gard JJ, Yamada K, Green KG et al (2005) Remodeling of gap junctions and slow conduction in a mouse model of desmin-related cardiomyopathy. Cardiovasc Res 67:539–547

    PubMed  CrossRef  CAS  Google Scholar 

  13. Zhuang J, Yamada KA, Saffitz JE et al (2000) Pulsatile stretch remodels cell-to-cell communication in cultured myocytes. Circ Res 87:316–322

    PubMed  CAS  Google Scholar 

  14. Pimentel RC, Yamada KA, Kléber AG et al (2002) Autocrine regulation of Cx43 expression by VEGF. Circ Res 90:671–677

    PubMed  CrossRef  CAS  Google Scholar 

  15. Yamada K, Green KG, Samarel AM et al (2005) Distinct pathways regulate expression of cardiac electrical and mechanical junctions proteins in response to stretch. Circ Res 97:346–353

    PubMed  CrossRef  CAS  Google Scholar 

  16. Conacci-Sorrell M, Zhurinsky J, Ben-Ze’ev A (2002) The cadherin-catenin adhesion system in signaling and cancer. J Clin Invest 109:987–991

    PubMed  CrossRef  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2007 Springer-Verlag Italia

About this chapter

Cite this chapter

Saffitz, J.E. (2007). Cell Adhesion Pathology. In: Markus, F.I., Nava, A., Thiene, G. (eds) Arrhythmogenic RV Cardiomyopathy/Dysplasia. Springer, Milano. https://doi.org/10.1007/978-88-470-0490-0_6

Download citation

  • DOI: https://doi.org/10.1007/978-88-470-0490-0_6

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-0489-4

  • Online ISBN: 978-88-470-0490-0

  • eBook Packages: MedicineMedicine (R0)