From cell phenotype to epigenetic mechanisms: new insights into regenerating myocardium

The self-regenerating property of the adult myocardium is not a new discovery. Even though we could not confirm that the adult myocardium is a post-mitotic tissue, we should consider that its plasticity is extremely low. Studies are still in progress to decipher the mechanisms underlying the abovementioned potential fetal features of the adult heart. The modest results of several clinical trials based on the transplantation of millions of autologous stem cells into the dysfunctional heart have confirmed that the cross-talk of different signals, such as the microenvironment, promotes the regeneration of adult myocardium. Recent scientific evidence has revealed that cellular cross-talk does not depend on the action of a single cell phenotype. It is conceivable that the limited turnover of cardiomyocytes is ensured by the interplay of adult cardiac cells in response to environmental changes. The epigenetic state of a cell serves as a dynamic interface between the environment and phenotype. The epigenetic modulation of the adult cardiac cells by natural active compounds encourages further studies to improve myocardial plasticity. In this review, we will highlight the most relevant studies demonstrating the epigenetic modulation of myocardial regeneration without the use of stem cell transplantation. Key words: epigenetic, myocardial regeneration, microenvironment, heart, stem cells. La propriete d'auto-regeneration du myocarde adulte n'est pas une nouvelle decouverte. Bien que nous ne puissions confirmer que le myocarde adulte est un tissu post-mitotique, nous devrions considerer sa plasticite comme extremement faible. Des etudes sont toujours en cours afin de decortiquer les mecanismes qui sous-tendent ces caracteristiques possiblement foetales du coeur adulte. Les resultats modestes de plusieurs essais cliniques bases sur la transplantation de millions de cellules souches autologues dans le coeur dysfonctionnel ont confirme que la communication croisee de differents signaux comme le microenvironnement favorise la regeneration du myocarde adulte. Des donnees scientifiques recentes ont revele que la communication croisee cellulaire ne depend pas de l'action d'un phenotype cellulaire unique. On peut concevoir que le renouvellement limite des cardiomyocytes soit assure par l'interaction de cellules cardiaques adultes en reponse a des changements environnementaux. L'etat epigenetique d'une cellule sert d'interface dynamique entre l'environnement et le phenotype. La modulation epigenetique des cellules cardiaques adultes par des composes naturels actifs nous encourage a realiser davantage d'etudes afin d'ameliorer la plasticite myocardique. Dans cet article de synthese, nous mettrons en evidence les etudes les plus pertinentes qui demontrent une modulation epigenetique de la regeneration myocardique sans utilisation de la transplantation de cellules souches. [Traduit par la Redaction] Mots-cles : epigenetique, regeneration myocardique, microenvironnement, coeur, cellules souches.
Introduction Up to 15 years ago, the adult myocardium was not widely considered a self-renewing tissue, even if the rare mitosis of adult cardiomyocytes was already detected in the human [...]