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Developmental signals and adult heart regeneration

  • Heart regeneration after cryoinjury in the zebrafish, presented by N Mercader (Madrid, ES)
  • Epicardial development in model systems, presented by T Brand (Harefield, GB) - Slides
  • The role of WT1 in regulating epicardial development, presented by J M Perez-Pomares (Malaga, ES) - Slides
  • Neovascularisation in the adult heart - involvement of the epicardium, presented by N Smart (London, GB) - Slides
Myocardial Disease

Heart function is orchestrated by multiple inputs. Biological insults affecting them can have profound effects on cardiac performance, leading initially to an adaptive response but eventually decompensating cardiac function. Unfortunately, the natural capacity of the adult heart to refurbish the damaged myocardium is very limited, and thus strategies to heal the heart are nowadays compulsory. Natural signalling pathways forming the heart during development will assist us to find suitable strategies as for example recent evidences demonstrating that epicardial precursors have the developmental potential to provide myocardial cells, which is nonetheless inhibited during normal embryonic development. Thus, unlocking these signals is revealed as a perfect way to regenerate the damaged heart since epicardial cells are already placed in the patient’s heart.

In this session, Prof. Thomas Brand nicely introduced the comparative developmental biology of the proepicardium, the epicardium precursors, and highlighted the distinct signalling pathways involved in epicardial development.

Bmp, Fgf and Notch signalling were revisited as well as new evidence of signal emanating from the liver anlage, in addition to the left-right signalling. Cell labelling experiments provided evidence of a heterogeneous contribution to the proepicardium, but evidence of whether such early heterogeneity is translated into distinct cell type contribution to the adult heart remains elusive.

In this context, Prof. Jose Maria Perez-Pomares provided a wonderful overview of the distinct cell contribution of the proepicardium to the adult heart, hitting on the species-specific differences and highlighting the pivotal role of Wt1 regulating several downstream signalling pathways, such as retinoic acid and pdgf. Proof-of-principle usage of epicardial layer as a regenerative tools came by with superb contributions from Dr. Nadia Mercader and Dr. Nicola Smart.

Dr. Mercader reported their latest findings using heart regeneration model after cryoinjury in the zebrafish heart, highlighting the instructive role of the epicardial derived cells to regenerate the damaged myocardium as well as to resume the initial fibrotic deposition. Dr. Smart reported the usage of thymosin beta4 as an instructive signal to the epicardium to heal the damaged mouse heart. In both contributions, understandings of the signalling pathways remain unclear but nicely exemplified the potential of the epicardium as a regenerative tool.




Developmental signals and adult heart regeneration

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.