Cardiac Regeneration

Cardiovascular diseases including congenital heart defects are the leading cause of mortality. Cardiac diseases result in myocyte deficiency that ultimately leads to congestive heart failure. Despite significant advances, conventional treatments do not correct the defects in myocyte numbers and the prognosis of congestive heart failure remains poor. For this reason, the replacement of lost cardiomyocytes is a primary target of regenerative medicine research.
Although recent studies have uncovered the remarkable regenerative capacity of the newborn mammalian heart, this regenerative potential is lost shortly after birth, strongly supporting the hypothesis that a detailed understanding of developmental mechanisms is essential to identify targets for cardiac repair or regeneration in congenital and acquired heart diseases. Triggering cell cycle re-entry of existing cardiomyocytes together with the stimulation of multipotent cardiac progenitor cells currently represent the most promising approaches for cardiac regeneration over the coming years.
Using a combination of state of the art molecular, developmental, physiological and transgenic approaches our group aims to enhance our knowledge of cardiac development and to contribute to a greater understanding of regulatory steps controlling cardiomyocyte proliferation and progenitor cell fate. Identifying how these process are regulated is thus of crucial importance in regenerative medicine and will inform future cardiac repair strategies.

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Hubert, F.  et al. 2021

FGF10 promotes cardiac repair through a dual cellular mechanism increasing cardiomyocyte renewal and inhibiting fibrosis

AIMS: Promoting cardiomyocyte renewal represents a major therapeutic approach for heart regeneration and repair. Our study aims to investigate the relevance of FGF10 as a potential target for heart...
Cardiovasc Res - issue: - volume: - pages: cvab340.

Moyon, A.  et al. 2021

Comparison of a New 68Ga-Radiolabelled PET Imaging Agent sCD146 and RGD Peptide for In Vivo Evaluation of Angiogenesis in Mouse Model of Myocardial Infarction

Ischemic vascular diseases are associated with elevated tissue expression of angiomotin (AMOT), a promising molecular target for PET imaging. On that basis, we developed an AMOT-targeting radiotracer,...
Cells - issue: 9 - volume: 10 - pages: 2305.

Payan, SM.  et al. 2020

Cardiomyocyte proliferation, a target for cardiac regeneration

Cardiac diseases, characterized by cardiomyocyte loss, lead to dramatic impairment of cardiac function and ultimately to congestive heart failure. Despite significant advances, conventional treatments...
Biochim Biophys Acta Mol Cell Res - issue: 3 - volume: 1867 - pages: 118461.

Payan, S.  et al. 2019

Cardiomyocyte proliferation, a target for cardiac regeneration

Cardiac diseases, characterized by cardiomyocyte loss, lead to dramatic impairment of cardiac function and ultimately to congestive heart failure. Despite significant advances, conventional treatments...
Biochim Biophys Acta Mol Cell Res - issue: - volume: - pages: .

Hubert, F.  et al. 2018

FGF10 Signaling in Heart Development, Homeostasis, Disease and Repair

Essential muscular organ that provides the whole body with oxygen and nutrients, the heart is the first organ to function during embryonic development. Cardiovascular diseases, including acquired and...
Front Genet - issue: - volume: 9 - pages: 599.

Ahles, A.  et al. 2015

Interhelical Interaction and Receptor Phosphorylation Regulate the Activation Kinetics of Different Human beta(1)-Adrenoceptor Variants

G protein-coupled receptors represent the largest class of drug targets, but genetic variation within G protein-coupled receptors leads to variable drug responses and, thereby, compromises their...
J. Biol. Chem. - issue: 3 - volume: 290 - pages: 1760-1769.

Rochais, F.  et al. 2014

FGF10 promotes regional foetal cardiomyocyte proliferation and adult cardiomyocyte cell-cycle re-entry

AIMS: Cardiomyocyte proliferation gradually declines during embryogenesis resulting in severely limited regenerative capacities in the adult heart. Understanding the developmental processes...
Cardiovasc. Res. - issue: 3 - volume: 104 - pages: 432-442.

Ahles, A.  et al. 2011

A polymorphism-specific "memory" mechanism in the β(2)-adrenergic receptor

Signaling through G protein (heterotrimeric guanosine triphosphate-binding protein)-coupled receptors is affected by polymorphisms in receptor-encoding genes. Using fluorescence resonance energy...
Sci Signal - issue: 185 - volume: 4 - pages: ra53.

Rochais, F.  et al. 2010

Acute cardiac effects of neuregulin-1/ErbB signalling


Cardiovasc. Res. - issue: 3 - volume: 88 - pages: 393-394.

Rochais, F.  et al. 2010

Acute cardiac effects of neuregulin-1/ErbB signalling


Cardiovasc Res - issue: 3 - volume: 88 - pages: 393-394.

Rochais, F.  et al. 2009

Hes1 is expressed in the second heart field and is required for outflow tract development

BACKGROUND: Rapid growth of the embryonic heart occurs by addition of progenitor cells of the second heart field to the poles of the elongating heart tube. Failure or perturbation of this process...
PLoS One - issue: 7 - volume: 4 - pages: e6267.

Rochais, F.  et al. 2009

Signaling pathways controlling second heart field development

Insight into the mechanisms underlying congenital heart defects and the use of stem cells for cardiac repair are major research goals in cardiovascular biology. In the early embryo, progenitor cells...
Circ Res - issue: 8 - volume: 104 - pages: 933-942.

Engelhardt, S.  et al. 2007

G proteins: more than transducers of receptor-generated signals?


Circ Res - issue: 8 - volume: 100 - pages: 1109-1111.

Rochais, F.  et al. 2007

Real-time optical recording of beta1-adrenergic receptor activation reveals supersensitivity of the Arg389 variant to carvedilol

Antagonists of beta-adrenergic receptors (beta-ARs) have become a main therapeutic regimen for the treatment of heart failure even though the mechanisms of their beneficial effects are still poorly...
J Clin Invest - issue: 1 - volume: 117 - pages: 229-235.

Hein, P.  et al. 2006

Gs activation is time-limiting in initiating receptor-mediated signaling

To analyze individual steps of G(S)-linked signaling in intact cells, we used fluorescence resonance energy transfer (FRET)-based assays for receptor-G protein interaction, G protein activation, and...
J Biol Chem - issue: 44 - volume: 281 - pages: 33345-33351.

Fischmeister, R.  et al. 2006

Compartmentation of cyclic nucleotide signaling in the heart: the role of cyclic nucleotide phosphodiesterases

A current challenge in cellular signaling is to decipher the complex intracellular spatiotemporal organization that any given cell type has developed to discriminate among different external stimuli...
Circ Res - issue: 8 - volume: 99 - pages: 816-828.

Vandecasteele, G.  et al. 2006

Functional localization of cAMP signalling in cardiac myocytes

The cAMP pathway is of cardinal importance for heart physiology and pathology. The spatial organization of the various components of the cAMP pathway is thought to allow the segregation of functional...
Biochem Soc Trans - issue: Pt 4 - volume: 34 - pages: 484-488.

Rochais, F.  et al. 2006

A specific pattern of phosphodiesterases controls the cAMP signals generated by different Gs-coupled receptors in adult rat ventricular myocytes

Compartmentation of cAMP is thought to generate the specificity of Gs-coupled receptor action in cardiac myocytes, with phosphodiesterases (PDEs) playing a major role in this process by preventing...
Circ Res - issue: 8 - volume: 98 - pages: 1081-1088.

Morel, E.  et al. 2005

cAMP-binding protein Epac induces cardiomyocyte hypertrophy

cAMP is one of the most important second messenger in the heart. The discovery of Epac as a guanine exchange factor (GEF), which is directly activated by cAMP, raises the question of the role of this...
Circ Res - issue: 12 - volume: 97 - pages: 1296-1304.

Fischmeister, R.  et al. 2005

Species- and tissue-dependent effects of NO and cyclic GMP on cardiac ion channels

Biochemical studies have established the presence of a NO pathway in the heart, including sources of NO and various effectors. Several cardiac ion channels have been shown to be modified by NO, such...
Comp Biochem Physiol A Mol Integr Physiol - issue: 2 - volume: 142 - pages: 136-143.

Rochais, F.  et al. 2004

Negative feedback exerted by cAMP-dependent protein kinase and cAMP phosphodiesterase on subsarcolemmal cAMP signals in intact cardiac myocytes: an in vivo study using adenovirus-mediated expression of CNG channels

Intracardiac cAMP levels are modulated by hormones and neuromediators with specific effects on contractility and metabolism. To understand how the same second messenger conveys different information,...
J Biol Chem - issue: 50 - volume: 279 - pages: 52095-52105.