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.

ATIP


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

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

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Nfatc1 Promotes Interstitial Cell Formation During Cardiac Valve Development in Zebrafish

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

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