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Cardiovascular medicine

Cardiovascular pathologies are one of the main causes of death in Western Countries and represent a major problem of public health. In the Cardiovascular Medicine (CVM) group cardiac diseases are assessed by a multidisciplinary approach involving cell biology/physiology and bioinformatics/biostatistics resources.
In this context, the aims of the group are:

  1. to explore basic epigenetic mechanisms responsible for the regulation of cardiac cell physiology as well as the molecular determinants of cardiac pathophysiology
  2. to establish human and murine functional cell models of cardiomyogenesis and cardiac disease (i.e. mouse haploid stem cells, human cardiac mesenchymal stromal cells, or CStC, human induced pluripotent stem cells, or iPSC – see Figure 1)
  3. to investigate the role of cells other than cardiomyocytes (i.e. cardiac mesenchymal-like stromal cells, or CStC -  see Figure 2) in the onset of cardiac diseases
  4. to prioritize candidate genes obtained by next generation sequencing and GWAS dataset analyses for detailed follow up in functional cell models​​

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Figure 1: Example of huma​n iPSC colony.

​Human induced pluripotent stem cells (iPSC) are a unique population of pluripotent cells that may be obtained from fibroblasts of individuals affected by different cardiac diseases such as long-QT syndrome. Similarly to ES cells, iPSC differentiate into cardiomyocytes under appropriate in vitro stimulation. Since cardiomyocytes c​​annot be isolated at high efficiency directly from patients, iPSC currently represent the best in vitro model to investigate in vitro human cardiomyogenesis, to recapitulate the features of genetic diseases and to perform pharmacological patient-tailored drug screening.​

Figure 2: CStC expressing the alpha-sarcomeric actin ​​​after in vitro cardiomyogenic treatment

​CStC are characterized by fibroblast morphology, phenotype and biological characteristics (such as fast growth kinetic, stress-fibres production under serum deprivation). Nevertheless, under appropriate stimulation, in vitro  they acquire some features of cardiomyocyte precursors, such as the  up-regulation of early (Nkx2.5, GATA4) and late (α-sarcomeric actin, NaV1.5; Vecellio M. et al., unpublished data) cardiac genes and the appearance of a fast sodium current. Further, in vivo, when injected in a rat model of myocardial infarction, they differentiate into adult-like cardiomyocytes. Therefore, due to their residual plasticity, CStC represent a cell type of possible interest for regenerative medicine application.

Recent evidences also suggest that the involvement of CStC in cardiac homeostasis may be greater than previously thought. In this light, the study of putative role of CStC in structural cardiac pathologies represents an important scientific question yet unanswered.​


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