Cardiovascular calcification

Cardiovascular calcification (CVC) is characterised by the progressive deposition of calcified matrix in blood vessels, cardiac valves and other heart tissues.  This alteration of the tissue impairs blood circulation and is associated with high morbidity and mortality.  The causes and risk factors associated with CVC are highly heterogeneous, making it particularly difficult to study and limiting therapy options.  In our lab we use zebrafish as a new model system to study CVC since it allows the direct observation of the calcification progress using live-imaging microscopy at single-cell resolution.  We are studying multiple genetic models to characterise the different cells contributing to calcification and identify new molecular factors regulating this process.  We are also particularly interested in understanding the functional impact of calcification in the tissue, and how it affects blood circulation.  We will use these genetic models to identify new therapeutic approaches to ameliorate the impact of CVC.

Cardiac Valve Regeneration

The cardiac valves are the structures that ensure unidirectional blood flow within the heart.  Congenital malformations or diseases manifested in adult life may impair this crucial role, leading to surgical intervention to reduce morbidity and mortality.  However, the success of bioprosthetic valve implants may be compromised by chronic inflammation or poor cellularization by the host cells, causing the degeneration of the tissue.

Most studies on valve implants is conducted in large animal models which show limited regenerative capacity.  We recently developed a new model to study cardiac valve regeneration taking advantage of the zebrafish ability to regenerate multiple organs and tissues after injury.  With this model we showed that genetic ablation of the valve cells triggers the initiation of a regenerative program mediated by TGFß signalling, leading to the formation of a new functional valve. 

We are now interested in understanding cell heterogeneity during the regenerative process, namely of the valve endothelium and immune cells, to understand their different contributions to the new valve.  With this approach we expect to identify new factors promoting valve regeneration relevant for the improvement of cardiac implants.


Gentile A., .  et al. 2021

The EMT transcription factor Snai1 maintains myocardial wall integrity by repressing intermediate filament gene expression.

The transcription factor Snai1, a well-known regulator of epithelial-to-mesenchymal transition, has been implicated in early cardiac morphogenesis as well as in cardiac valve formation. However, a...
eLife - issue: - volume: 10 - pages: e66143.

Boezio GL., .  et al. 2020

Endothelial TGF-β signaling instructs smooth muscle cell development in the cardiac outflow tract

The development of the cardiac outflow tract (OFT), which connects the heart to the great arteries, relies on a complex crosstalk between endothelial (ECs) and smooth muscle (SMCs) cells. Defects in...
eLife - issue: - volume: 9 - pages: e57603.

Gunawan F., .  et al. 2020

Nfatc1 Promotes Interstitial Cell Formation During Cardiac Valve Development in Zebrafish

Rationale: The transcription factor NFATC1 (nuclear factor of activated T-cell 1) has been implicated in cardiac valve formation in humans and mice, but we know little about the underlying mechanisms....
Circ Res - issue: 126 - volume: 8 - pages: 968-984.

Bensimon-Brito A., .  et al. 2020

TGF-β Signaling Promotes Tissue Formation during Cardiac Valve Regeneration in Adult Zebrafish

Cardiac valve disease can lead to severe cardiac dysfunction and is thus a frequent cause of morbidity and mortality. Its main treatment is valve replacement, which is currently greatly limited by the...
Dev Cell - issue: 52 - volume: 1 - pages: 9-20.e7.

Brandão AS., .  et al. 2019

Yap induces osteoblast differentiation by modulating Bmp signalling during zebrafish caudal fin regeneration

Osteoblast differentiation is a key process for bone homeostasis and repair. Multiple signalling pathways have been associated with osteoblast differentiation, yet much remains unknown on how this...
J Cell Sci - issue: 132 - volume: 22 - pages: jcs231993.

Bensimon-Brito A., .  et al. 2016

Revisiting in vivo staining with alizarin red S-a valuable approach to analyse zebrafish skeletal mineralization during development and regeneration

Background: The correct evaluation of mineralization is fundamental for the study of skeletal development, maintenance, and regeneration. Current methods to visualize mineralized tissue in zebrafish...
BMC Dev Biol - issue: 16:02 - volume: - pages: .

Simões MG., .  et al. 2014

Denervation impairs regeneration of amputated zebrafish fins

Background: Zebrafish are able to regenerate many of its tissues and organs after damage. In amphibians this process is regulated by nerve fibres present at the site of injury, which have been...
BMC Dev Biol - issue: - volume: - pages: 14:49.

Bensimon-Brito A., .  et al. 2012

Distinct patterns of notochord mineralization in zebrafish coincide with the localization of Osteocalcin isoform 1 during early vertebral centra formation

Background: In chondrichthyans, basal osteichthyans and tetrapods, vertebral bodies have cartilaginous anlagen that subsequently mineralize (chondrichthyans) or ossify (osteichthyans). Chondrocytes...
BMC Dev Biol - issue: 12:28 - volume: - pages: .