• Le 27 February 2020
    Institut de Recherche en Santé - 8 quai Moncousu - Nantes
    Amphithéâtre Denis Escande
  • 13h00

Titre de la thèse : Cardiac pathophysiology related to calcium handling disorders and pharmacological approaches

Equipe

Equipe IIa - Canaux ioniques et arythmies cardiaques


Directeur de thèse

Patricia LEMARCHAND

Co-directeur

Michel DE WAARD

Co-encadrant

Nathalie GABORIT


Jury

  • Ana-Maria GOMEZ - DR - Université Paris-Sud - UMR1180 (rapporteur)
  • Jérémy FAUCONNIER, CR - Université de Montpellier - U1046 - PhyMedExp (rapporteur)
  • Mattéo MANGONI - DR - Université de Montpellier - UMR 5203 - Institut de Génomique Fonctionnelle (examinateur)


Résumé

Heart rhythm disorders represent a leading cause of death worldwide. They have been extensively associated with impaired cellular excitability and disrupted calcium handling. Hence, study of pathophysiological mechanisms involved in these cardiac arrhythmias constitute one of the major challenges of current research. In this context, human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) stand as a reliable and extremely relevant tool to model these pathologies. In addition to representing an inexhaustible source of different genetic models, they pave the way for a more personalized medicine, allowing for the implementation of more precise and more appropriate pharmacological responses.
Part of the approaches used on these integrated models are based on the development of pharmacological tools allowing for fine tuning of the cellular excitability. A tremendous pharmacological diversity is provided by natural peptides which can modulate contributors to this excitability in a highly potent and a highly selective way. In the present work, these tools allowed us to investigate the role of these contributors in our model. Furthermore, we were able to highlight anti-arrhythmic effects of a natural modulator of ryanodine receptor through the study of two novel genetic variants implicated in catecholaminergic polymorphic ventricular tachycardia (CPVT). Altogether, this study emphasizes the importance of these approaches for the development of new therapeutic avenues in the context of heart rhythm disorders.