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Unmasking the molecular link between arrhythmogenic cardiomyopathy and Brugada syndrome

Nature Reviews Cardiology volume 14, pages 744–756 (2017)Cite this article

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Abstract

The intercalated discs that connect cardiomyocytes control cell-to-cell adhesion and communication. Several macromolecular structures (desmosomes, fascia adherens junctions, gap junctions, and sodium-channel complexes) coexist in, and confer their mechanical and electrical properties to, the intercalated disc. Traditionally, each structure was assumed to have a unique function in the intercalated disc. However, growing evidence suggests that these complexes act together in intercellular communication and adhesion, forming a single structural and functional entity — the connexome. This nascent idea has provided conceptual support for the overlapping of two diseases based on disturbance of the intercalated disc — arrhythmogenic cardiomyopathy (ACM) and Brugada syndrome (BrS). In this Perspectives article, we present the latest findings about the functions of, and interactions between, the structures of the intercalated disc that support the concept of the connexome. We also summarize the genetic, molecular, and pathophysiological mechanisms underlying ACM and BrS, focusing on the overlap between these diseases.

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Figure 1: The components of the intercalated disc.
Figure 2: Genes associated with arrhythmogenic cardiomyopathy and Brugada syndrome.
Figure 3: Distribution of structures in the intercalated disc of cardiomyocytes.
Figure 4: Intercalated disc maturation.
Figure 5: Molecular and cellular effects of PKP2.
Figure 6: Factors modulating SCN5A gene expression.
Figure 7: Proposed mechanisms of arrhythmogenic cardiomyopathy and Brugada syndrome.

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Acknowledgements

The authors are supported by grants from Obra Social “la Caixa”, and Fundació Marató TV3-2014, Catalonia, Spain.

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Authors and Affiliations

  1. Javier Moncayo-Arlandi is at the Cardiovascular Genetics Centre, Girona Institute of Biomedical Research (IDIBGI), Carrer del Dr. Castany, s/n, 17190 Salt, Girona, Spain.,

    Javier Moncayo-Arlandi

  2. Spain; the Medical Science Department, Ramon Brugada is at the Cardiovascular Genetics Centre, Institut d'Investigació Biomèdica Girona (IDIBGI), University of Girona, Carrer del Dr. Castany, s/n, Parc Hospitalari Martí i Julià (M-2), 17190 Salt, Girona, School of Medicine, University of Girona, Plaça de Sant Domènec, 3, 17004 Girona, Girona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Avenida Monforte de Lemos, 3–5, 28029 Madrid, Spain; and the Cardiology Service, Hospital Josep Trueta, Avinguda de França, s/n, 17007 Girona, Girona, Spain.,

    Ramon Brugada

  3. the Medical Science Department, School of Medicine, University of Girona, Plaça de Sant Domènec, 3, 17004 Girona, Girona, Spain,

    Ramon Brugada

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  1. Javier Moncayo-Arlandi
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J.M.-A. researched data for the article. Both authors discussed the content of the article, wrote the manuscript, and reviewed and edited it before submission.

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Correspondence to Javier Moncayo-Arlandi or Ramon Brugada.

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Moncayo-Arlandi, J., Brugada, R. Unmasking the molecular link between arrhythmogenic cardiomyopathy and Brugada syndrome. Nat Rev Cardiol 14, 744–756 (2017). https://doi.org/10.1038/nrcardio.2017.103

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