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(Mal)adaptative beta-adrenergic regulation of the cardiac voltage-gated sodium channel, Nav1.5

Objective

Cardiovascular disease is a leading cause of morbidity and mortality in Europe and, in the face of population aging, this statistic is predicted to significantly worsen. One of the major CVD risk factors is represented by the alterations of beta-adrenergic receptors stimulation, which modulates the function of the voltage-gated sodium channel, Nav1.5 in cardiomyocytes. In a healthy heart, beta-adrenergic receptors regulate the function of Nav1.5 to potentiate cardiac contraction during common everyday activities like physical exercise. However, the same pathway promotes and worsens cardiovascular disease such as heart failure. Thus, there is an urgent need to investigate how a healthy physiological response becomes deleterious in order to better understand cardiovascular disease occurrence and hence to improve its treatment. MALBENA will address this challenge through an ambitious and interdisciplinary study that will thoroughly assess molecular and functional modifications of Nav1.5 in the beta-adrenergic receptor-stimulated cardiomyocytes as well as in human failing and non-failing hearts. Such profiling of the physiological and pathological remodeling of Nav1.5 will provide a substantial impact on the novel strategies developing targeted therapies aiming to reduce the cardiovascular disease burden and, at the same time, having little to no side effects on the other organs, since Nav1.5 is nearly exclusive to cardiomyocytes. The combination of unique expertises of the host supervisor, Dr. Céline Marionneau, in phosphoproteomics of Nav1.5 and of the researcher, Dr. Oksana Iamshanova, in Nav1.5 functioning as the macromolecular complex, will enable synergistic implementation of the scientific backgrounds, techniques, and methods to guarantee the successful achievement of MALBENA’s objectives.

Fields of science (EuroSciVoc)

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INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
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€ 242 260,56
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RUE DE TOLBIAC 101
75654 Paris
France

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Ile-de-France Ile-de-France Paris
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