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Animal models of arrhythmogenic right ventricular cardiomyopathy: what have we learned and where do we go? Insight for therapeutics

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Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetically-determined cardiac heart muscle disorder characterized by fibro-fatty replacement of the myocardium that results in heart failure and sudden cardiac death (SCD), predominantly in young males. The disease is often caused by mutations in genes encoding proteins of the desmosomal complex, with a significant minority caused by mutations in non-desmosomal proteins. Existing treatment options are based on SCD prevention with the implantable cardioverter defibrillator, antiarrhythmic drugs, and anti-heart failure medication. Heart transplantation may also be required and there is currently no cure. Several genetically modified animal models have been developed to characterize the disease, assess its progression, and determine the influence of potential environmental factors. These models have also been very valuable for translational therapeutic approaches, to screen new treatment options that prevent and/or reverse the disease. Here, we review the available ARVC animal models reported to date, highlighting the most important pathophysiological findings and discussing the effect of treatments tested so far in this setting. We also describe gaps in our knowledge of the disease, with the goal of stimulating research and improving patient outcomes.

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Acknowledgements

We gratefully acknowledge Kenneth McCreath, PhD, for English editing.

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Author notes

  1. Laura Padrón-Barthe and Fernando Domínguez contributed equally to this work.

Authors and Affiliations

  1. CIBER Cardiovascular Diseases (CIBERCV), Madrid, Spain

    Laura Padrón-Barthe, Fernando Domínguez, Pablo Garcia-Pavia & Enrique Lara-Pezzi

  2. Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Manuel de Falla, 2, Majadahonda, 28222, Madrid, Spain

    Fernando Domínguez & Pablo Garcia-Pavia

  3. Francisco de Vitoria University, Madrid, Spain

    Pablo Garcia-Pavia

  4. Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor Fernandez Almagro, 3, 28029, Madrid, Spain

    Enrique Lara-Pezzi

  5. Faculty of Medicine, National Heart and Lung Institute, Imperial College, London, UK

    Enrique Lara-Pezzi

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  1. Laura Padrón-Barthe
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  2. Fernando Domínguez
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  3. Pablo Garcia-Pavia
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  4. Enrique Lara-Pezzi
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Corresponding authors

Correspondence to Pablo Garcia-Pavia or Enrique Lara-Pezzi.

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The authors declare that they have no conflicts of interest with the contents of this article.

Funding

This work was supported in part by the Instituto de Salud Carlos III (ISCIII) [Grants PI14/0967, and RD012/0042/0066], the Todos somos Raros program [Grant to PG-P], and the Spanish Society of Cardiology [2014 Basic Research Grant to PG-P]. ISCIII grants are supported by the Plan Estatal de I + D+I 2013-2016—European Regional Development Fund (FEDER) “A way of making Europe”.

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Padrón-Barthe, L., Domínguez, F., Garcia-Pavia, P. et al. Animal models of arrhythmogenic right ventricular cardiomyopathy: what have we learned and where do we go? Insight for therapeutics. Basic Res Cardiol 112, 50 (2017). https://doi.org/10.1007/s00395-017-0640-3

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