A heart to last a lifetime: countering the effects of congenital and acquired cardiovascular diseases

The heart is the first functional organ in vertebrates and beats more than 3 billions times over the lifespan. It delivers nutrients and oxygen at all stages of life. Developmental defects are associated with a wide class of malformations named congenital heart defects. Collectively, congenital heart defects are the most common type of birth defect, affecting almost 1% of newborn children. Late-onset cardiovascular diseases leading to heart failure are the number one cause of death in adulthood. Understanding normal and pathological cardiovascular development, from the earliest stages through the formation of the fully developed cardiovascular system, is necessary for identifying the causes of congenital heart defect and developing therapeutic strategies for cardiac repair.

Initial cardiovascular system morphogenesis requires complex genetic and epigenetic processes involving diverse types of progenitor cells which interact with each other. The DevCard department, composed of three laboratories (Michel Pucéat, Francesca Rochais and Stéphane Zaffran), is dedicated to study molecular and cellular mechanisms required for normal and pathological cardiac development and function. Therefore, using mouse, chick, human and embryonic stem cell models, these laboratories aim to identify crucial regulatory networks operating in the developing heart, blood vessels, and valvular system but also during heart regeneration and repair.



European Society of Cardiology
Groupe de Réflexion sur la Recherche Cardiovasculaire
The Heart Valve Societe
Société Française de Biologie du Développement
Société de Biologie Cellulaire de France
Société Française de Cardiologie
Filière Santé Maladies Rares TeteCou

Stefanovic, S.  et al. 2017

Mechanisms of retinoic acid signaling during cardiogenesis

Substantial experimental and epidemiological data have highlighted the interplay between nutritional and genetic factors in the development of congenital heart defects. Retinoic acid (RA), a...
Mech. Dev. - issue: - volume: 143 - pages: 9-19.

Roux, M.  et al. 2017

Hoxa1 and Hoxb1 are required for pharyngeal arch artery development

Hox transcription factors play critical roles during early vertebrate development. Previous studies have revealed an overlapping function of Hoxa1 and Hoxb1 during specification of the rhombomeres...
Mech. Dev. - issue: - volume: 143 - pages: 1-8.

Theron, A.  et al. 2016

An uncommon cause of tricuspid regurgitation: three-dimensional echocardiographic incremental value, surgical and genetic insights

Congenital tricuspid valve disease is a rare defect that includes regurgitation, stenosis and Ebstein's anomaly. We report a case of severe tricuspid regurgitation associated with functional mitral...
Eur. J. Cardio-Thorac. Surg. - issue: 1 - volume: 50 - pages: 180-182.

Sturny, R.  et al. 2016

FGF10 is required to promote cardiomyocyte proliferation after myocardial infarction

Cardiovasc. Res. - issue: - volume: 111 - pages: S3-S3.

Rampersad, SN.  et al. 2016

Adaptive phenotypic modulation of human arterial endothelial cells to fluid shear stress-encoded signals: modulation by phosphodiesterase 4D-VE-cadherin signalling

Although cAMP-signalling regulates numerous functions of vascular endothelial cells (VECs), including their ability to impact vascular resistance in response to changes in blood flow dynamics, few of...
Cell. Signal. - issue: 7 - volume: 28 - pages: 741-748.

Roux, M.  et al. 2016

Hox Genes in Cardiovascular Development and Diseases

Congenital heart defects (CHD) are the leading cause of death in the first year of life. Over the past 20 years, much effort has been focused on unraveling the genetic bases of CHD. In particular,...
J. Dev. Biol. - issue: 2 - volume: 4 - pages: 14.

Rampersad, SN.  et al. 2016

EPAC1 promotes adaptive responses in human arterial endothelial cells subjected to low levels of laminar fluid shear stress: Implications in flow-related endothelial dysfunction

Blood flow-associated fluid shear stress (FSS) dynamically regulates the endothelium's ability to control arterial structure and function. While arterial endothelial cells (AEC) subjected to high...
Cell. Signal. - issue: 6 - volume: 28 - pages: 606-619.

Chassaing, N.  et al. 2016

Targeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network

Ocular developmental anomalies (ODA) such as anophthalmia/microphthalmia (AM) or anterior segment dysgenesis (ASD) have an estimated combined prevalence of 3.7 in 10,000 births. Mutations in SOX2 are...
Genome Res. - issue: 4 - volume: 26 - pages: 474-485.

El Robrini, N.  et al. 2016

Cardiac outflow morphogenesis depends on effects of retinoic acid signaling on multiple cell lineages

Background: Retinoic acid (RA), the bioactive derivative of vitamin A, is essential for vertebrate heart development. Both excess and reduced RA signaling lead to cardiovascular malformations...
Dev. Dyn. - issue: 3 - volume: 245 - pages: 388-401.

Theron, A.  et al. 2016

Krox20 heterozygous mice: A model of aortic regurgitation associated with decreased expression of fibrillar collagen genes

Background. - The mechanism involved in the onset of aortic valve (AoV) disease remains unclear despite its poor prognosis and frequency. Recently, we reported that Krox20 (EGR2 in humans) is involved...
Arch. Cardiovasc. Dis. - issue: 3 - volume: 109 - pages: 188-198.

Smith, PM.  et al. 2016

Leptin influences the excitability of area postrema neurons

The area postrema (AP) is a circumventricular organ with important roles in central autonomic regulation. This medullary structure has been shown to express the leptin receptor and has been suggested...
Am. J. Physiol.-Regul. Integr. Comp. Physiol. - issue: 5 - volume: 310 - pages: R440-R448.

Escot, S.  et al. 2016

Disruption of CXCR4 signaling in pharyngeal neural crest cells causes DiGeorge syndrome-like malformations

DiGeorge syndrome (DGS) is a congenital disease causing cardiac outflow tract anomalies, craniofacial dysmorphogenesis, thymus hypoplasia, and mental disorders. It results from defective development...
Development - issue: 4 - volume: 143 - pages: 582-588.

Stefanovic, S.  et al. 2015

GATA-dependent transcriptional and epigenetic control of cardiac lineage specification and differentiation

Heart progenitor cells differentiate into various cell types including pacemaker and working cardiomyocytes. Cell-type specific gene expression is achieved by combinatorial interactions between...
Cell. Mol. Life Sci. - issue: 20 - volume: 72 - pages: 3871-3881.

Roux, M.  et al. 2015

Hoxb1 regulates proliferation and differentiation of second heart field progenitors in pharyngeal mesoderm and genetically interacts with Hoxa1 during cardiac outflow tract development

Outflow tract (OFT) anomalies are among the most common congenital heart defects found at birth. The embryonic OFT grows by the progressive addition of cardiac progenitors, termed the second heart...
Dev. Biol. - issue: 2 - volume: 406 - pages: 247-258.

Durst, R.  et al. 2015

Mutations in DCHS1 cause mitral valve prolapse

Mitral valve prolapse (MVP) is a common cardiac valve disease that affects nearly 1 in 40 individuals(1-3). It can manifest as mitral regurgitation and is the leading indication for mitral valve...
Nature - issue: 7567 - volume: 525 - pages: 109-+.

Moore-Morris, T.  et al. 2015

Cardiac fibroblasts: from development to heart failure

Cardiac fibroblasts are a major cell population of the heart and are characterized by their capacity to produce extracellular matrix (ECM). In hearts subjected to pressure overload, excessive...
J. Mol. Med. - issue: 8 - volume: 93 - pages: 823-830.

Papoutsi, T.  et al. 2015

Msx1(creERT2) knock-In allele: A useful tool to target embryonic and adult cardiac valves

Heart valve development begins with the endothelial-to-mesenchymal transition (EMT) of endocardial cells. Although lineage studies have demonstrated contributions from cardiac neural crest and...
Genesis - issue: 5 - volume: 53 - pages: 337-345.

Leschik, J.  et al. 2015

A View of Bivalent Epigenetic Marks in Two Human Embryonic Stem Cell Lines Reveals a Different Cardiogenic Potential

Human embryonic stem (HUES) cells are derived from early individual embryos with unique genetic printing. However, how their epigenetic status might affect their potential to differentiate toward...
Stem Cells Dev. - issue: 3 - volume: 24 - pages: 384-392.

Price, HN.  et al. 2015

Practical Application of the New Classification Scheme for Congenital Melanocytic Nevi

A new consensus-based classification of congenital melanocytic nevi (CMN) has recently been proposed. It includes categories for projected adult size (PAS) and location, satellite nevi counts, and...
Pediatr. Dermatol. - issue: 1 - volume: 32 - pages: 23-27.

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.

Hamdi, H.  et al. 2014

Long-Term Functional Benefits of Epicardial Patches as Cell Carriers

Both enzymatic dissociation of cells prior to needle-based injections and poor vascularization of myocardial infarct areas are two important contributors to cell death and impede the efficacy of...
Cell Transplant. - issue: 1 - volume: 23 - pages: 87-96.

Odelin, G.  et al. 2014

Loss of Krox20 results in aortic valve regurgitation and impaired transcriptional activation of fibrillar collagen genes

Aims Heart valve maturation is achieved by the organization of extracellular matrix (ECM) and the distribution of valvular interstitial cells. However, the factors that regulate matrix components...
Cardiovasc. Res. - issue: 3 - volume: 104 - pages: 443-455.

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 controlling...
Cardiovasc. Res. - issue: 3 - volume: 104 - pages: 432-442.

Richart, A.  et al. 2014

MicroRNA-21 Coordinates Human Multipotent Cardiovascular Progenitors Therapeutic Potential

Published clinical trials in patients with ischemic diseases show limited benefit of adult stem cell-based therapy, likely due to their restricted plasticity and commitment toward vascular cell...
Stem Cells - issue: 11 - volume: 32 - pages: 2908-2922.

Mohan, RA.  et al. 2014

A Mutation in the Kozak Sequence of GATA4 Hampers Translation in a Family With Atrial Septal Defects

Atrial septal defect (ASD) is the most common congenital heart defect clinically characterized by an opening in the atrial septum. Mutations in GATA4, TBX5, and NKX2-5 underlie this phenotype. Here,...
Am. J. Med. Genet. A - issue: 11 - volume: 164 - pages: 2732-2738.

Sussman, MA.  et al. 2014

Response to Letter Regarding Article, "Embryonic Stem Cell-Derived Cardiac Myocytes Are Not Ready for Human Trials"

Circ.Res. - issue: 10 - volume: 115 - pages: E30-E31.

Rana, MS.  et al. 2014

Tbx1 Coordinates Addition of Posterior Second Heart Field Progenitor Cells to the Arterial and Venous Poles of the Heart

Rationale: Cardiac progenitor cells from the second heart field (SHF) contribute to rapid growth of the embryonic heart, giving rise to right ventricular and outflow tract (OFT) myocardium at the...
Circ.Res. - issue: 9 - volume: 115 - pages: 790-U118.

Prados, B.  et al. 2014

Bmp2 patterns prospective valve tissue and regulates EMT and mesenchyme proliferation and morphogenesis

Transgenic Res. - issue: 5 - volume: 23 - pages: 901-901.

Moore-Morris, T.  et al. 2014

Targeting cardiac fibroblasts: The pressure is on

Cell Cycle - issue: 17 - volume: 13 - pages: 2647-2648.

Bertrand, N.  et al. 2014

LRRC1 and SCRIB, two polarity genes from the LAP family, genetically interact during embryogenesis

FEBS J. - issue: - volume: 281 - pages: 329-329.

Anderson, ME.  et al. 2014

Embryonic Stem Cell-Derived Cardiac Myocytes Are Not Ready for Human Trials

Circ.Res. - issue: 3 - volume: 115 - pages: 335-338.

Rochais, F.  et al. 2014

FGF10 regulates regional proliferation in the fetal heart through a FOXO3/p27kip1 pathway and promotes cell cycle reentry of adult cardiomyocytes

Cardiovasc. Res. - issue: - volume: 103 - pages: .

Maurice, DH.  et al. 2014

Cyclic nucleotide phosphodiesterases (PDEs): coincidence detectors acting to spatially and temporally integrate cyclic nucleotide and non-cyclic nucleotide signals

The cyclic nucleotide second messengers cAMP and cGMP each affect virtually all cellular processes. Although these hydrophilic small molecules readily diffuse throughout cells, it is remarkable that...
Biochem. Soc. Trans. - issue: - volume: 42 - pages: 250-256.

Hiriart, E.  et al. 2014

Cell Labeling and Injection in Developing Embryonic Mouse Hearts

Testing the fate of embryonic or pluripotent stem cell-derivatives in in vitro protocols has led to controversial outcomes that do not necessarily reflect their in vivo potential. Preferably, these...
J. Vis. Exp. - issue: 86 - volume: - pages: e51356.

Stefanovic, S.  et al. 2014

GATA-dependent regulatory switches establish atrioventricular canal specificity during heart development

The embryonic vertebrate heart tube develops an atrioventricular canal that divides the atrial and ventricular chambers, forms atrioventricular conduction tissue and organizes valve development. Here...
Nat. Commun. - issue: - volume: 5 - pages: 3680.

Etchevers, HC.  et al. 2014

Hiding in Plain Sight: Molecular Genetics Applied to Giant Congenital Melanocytic Nevi

Large and giant congenital melanocytic nevi are rare malformations that offer surprising insight into prenatal and postnatal acquisition of nevi of any size, central and peripheral nervous system...
- issue: 4 - volume: 134 - pages: 879-882.

Maurice, DH.  et al. 2014

Cyclic nucleotide phosphodiesterases (PDEs): coincidence detectors acting to spatially and temporally integrate cyclic nucleotide and non-cyclic nucleotide signals

The cyclic nucleotide second messengers cAMP and cGMP each affect virtually all cellular processes. Although these hydrophilic small molecules readily diffuse throughout cells, it is remarkable that...
Biochem. Soc. Trans. - issue: - volume: 42 - pages: 250-256.

Ahles, A.  et al. 2014

The Arg389Gly polymorphism determines structure and activation kinetics of the human beta(1)-adrenergic receptor

Naunyn-Schmiedebergs Arch. Pharmacol. - issue: - volume: 387 - pages: S24-S24.

Puceat, M.  et al. 2013

Could a pluripotent stem cell give rise to a high yield of a single cell lineage: a myocardial cell?

Curr. Opin. Genet. Dev. - issue: 4 - volume: 23 - pages: 498-499.

Catelain, C.  et al. 2013

Myoblasts and Embryonic Stem Cells Differentially Engraft in a Mouse Model of Genetic Dilated Cardiomyopathy

The functional and architectural benefits of embryonic stem cells (ESC) and myoblasts (Mb) transplantations into infarcted myocardium have been investigated extensively. Whereas ESC repopulated...
Mol. Ther. - issue: 5 - volume: 21 - pages: 1064-1075.

Puceat, M.  et al. 2013

Embryological origin of the endocardium and derived valve progenitor cells: From developmental biology to stem cell-based valve repair

The cardiac valves are targets of both congenital and acquired diseases. The formation of valves during embryogenesis (i.e., valvulogenesis) originates from endocardial cells lining the myocardium....
Biochim. Biophys. Acta-Mol. Cell Res. - issue: 4 - volume: 1833 - pages: 917-922.

Ahles, A.  et al. 2013

Phosphorylation-dependent receptor memory of the human beta(1)-adrenergic receptor

Naunyn-Schmiedebergs Arch. Pharmacol. - issue: - volume: 386 - pages: S3-S3.

Yajima, I.  et al. 2013

A Subpopulation of Smooth Muscle Cells, Derived from Melanocyte-Competent Precursors, Prevents Patent Ductus Arteriosus

Background: Patent ductus arteriosus is a life-threatening condition frequent in premature newborns but also present in some term infants. Current mouse models of this malformation generally lead to...
PLoS One - issue: 1 - volume: 8 - pages: e53183.

Van Vliet, P.  et al. 2012

Early cardiac development: a view from stem cells to embryos

From the 1920s, early cardiac development has been studied in chick and, later, in mouse embryos in order to understand the first cell fate decisions that drive specification and determination of the...
Cardiovasc. Res. - issue: 3 - volume: 96 - pages: 352-362.

Watanabe, Y.  et al. 2012

Fibroblast growth factor 10 gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic switch for down-regulation in the myocardium

During cardiogenesis, Fibroblast Growth Factor (Fgf10) is expressed in the anterior second heart field. Together with Fibroblast growth factor 8 (Fgf8), Fgf10 promotes the proliferation of these...
Proc. Natl. Acad. Sci. U. S. A. - issue: 45 - volume: 109 - pages: 18273-18280.

Zhai, K.  et al. 2012

beta-Adrenergic cAMP Signals Are Predominantly Regulated by Phosphodiesterase Type 4 in Cultured Adult Rat Aortic Smooth Muscle Cells

Background: We investigated the role of cyclic nucleotide phosphodiesterases (PDEs) in the spatiotemporal control of intracellular cAMP concentrations in rat aortic smooth muscle cells (RASMCs)....
PLoS One - issue: 10 - volume: 7 - pages: e47826.

Faure, E.  et al. 2012

P2Y2 receptor inhibits EGF-induced MAPK pathway to stabilise keratinocyte hemidesmosomes

alpha 6 beta 4 integrin is the main component of hemidesmosomes (HD) that stably anchor the epithelium to the underlying basement membrane. Epithelial cell migration requires HD remodelling, which can...
J. Cell Sci. - issue: 18 - volume: 125 - pages: 4264-4277.

Krupp, DR.  et al. 2012

Transcriptome profiling of genes involved in neural tube closure during human embryonic development using long serial analysis of gene expression (long-SAGE)

BACKGROUND Neural tube defects (NTDs) are common human birth defects with a complex etiology. To develop a comprehensive knowledge of the genes expressed during normal neurulation, we established...
Birth Defects Res. Part A-Clin. Mol. Teratol. - issue: 9 - volume: 94 - pages: 683-692.

Calderon, D.  et al. 2012

Immune response to human embryonic stem cell-derived cardiac progenitors and adipose-derived stromal cells

Transplantation of allogeneic human embryonic stem cell-derived cardiac progenitors triggers an immune response. We assessed whether this response could be modulated by the concomitant use of...
J. Cell. Mol. Med. - issue: 7 - volume: 16 - pages: 1544-1552.

Zaffran, S.  et al. 2012

New developments in the second heart field

During cardiac looping the heart tube elongates by addition of progenitor cells from adjacent pharyngeal mesoderm to the arterial and venous poles. This cell population, termed the second heart field,...
Differentiation - issue: 1 - volume: 84 - pages: .

Boon, R.  et al. 2012

A Day in the Life of a Young Investigator

Circulation - issue: 25 - volume: 125 - pages: F145-F150.

Chassaing, N.  et al. 2012

OTX2 mutations contribute to the otocephaly-dysgnathia complex

Background Otocephaly or dysgnathia complex is characterised by mandibular hypoplasia/agenesis, ear anomalies, microstomia, and microglossia; the molecular basis of this developmental defect is...
J. Med. Genet. - issue: 6 - volume: 49 - pages: 373-379.

Bun, S.  et al. 2012

Value of In Vivo T2 Measurement for Myocardial Fibrosis Assessment in Diabetic Mice at 11.75 T

Objective: The aim of the study was to assess the value of in vivo T2 measurements to noninvasively quantify myocardial fibrosis in diabetic mice at 11.75 T. Diabetic cardiomyopathy is characterized...
Invest. Radiol. - issue: 5 - volume: 47 - pages: 319-323.

Taylor, J.  et al. 2012

Cardiovascular Research Funding: European Molecular Biology Organization Awards

Circulation - issue: 14 - volume: 125 - pages: F79-F83.

Rochais, F.  et al. 2012

Fgf10 regulates fetal cardiac growth

Cardiovasc. Res. - issue: - volume: 93 - pages: S97-S97.

Ahles, A.  et al. 2012

The Gly389Arg polymorphism determines the activation kinetics of the human beta(1)-adrenergic receptor

Naunyn-Schmiedebergs Arch. Pharmacol. - issue: - volume: 385 - pages: 4-4.

Van Der Werf, CS.  et al. 2012

CLMP Is Required for Intestinal Development, and Loss-of-Function Mutations Cause Congenital Short-Bowel Syndrome

BACKGROUND & AIMS: Short-bowel syndrome usually results from surgical resection of the small intestine for diseases such as intestinal atresias, volvulus, and necrotizing enterocolitis. Patients with...
Gastroenterology - issue: 3 - volume: 142 - pages: 453-U98.

Goebel, P.  et al. 2012

Identification of novel targets of beta-adrenergic signaling through phosphoproteomics of the heart in vivo

Naunyn-Schmiedebergs Arch. Pharmacol. - issue: - volume: 385 - pages: 29-30.

Paris, M.  et al. 2012

Regulation of skin aging and heart development by TAp63

Since the discovery of the TP63 gene in 1998, many studies have demonstrated that Delta Np63, a p63 isoform of the p53 gene family, is involved in multiple functions during skin development and in...
Cell Death Differ. - issue: 2 - volume: 19 - pages: 186-193.

Golzio, C.  et al. 2012

ISL1 Directly Regulates FGF10 Transcription during Human Cardiac Outflow Formation

The LIM homeodomain gene Islet-1 (ISL1) encodes a transcription factor that has been associated with the multipotency of human cardiac progenitors, and in mice enables the correct deployment of second...
PLoS One - issue: 1 - volume: 7 - pages: e30677.