Cardiovascular diseases are the leading cause of death worldwide. Despite current treatments, the prognosis of heart failure is poor: approximately 50% of patients die within 5 years of diagnosis. Adult human hearts cannot produce new cardiomyocytes (i.e. heart muscle cells) to replace those that die upon injury, such as a myocardial infarction, leading to maladaptation of the remaining ventricular tissue (pathological remodelling) and eventually to heart failure.
Therapies that would promote regeneration of the injured myocardium would revolutionize the treatment of ischemic heart disease and heart failure. Remarkably, zebrafish and neonatal rodents can regenerate their hearts after an injury through revascularization of the injured area by angiogenesis (i.e. proliferation and migration of vascular endothelial cells) and renewal of the injured heart muscle by proliferation of cardiomyocytes. While zebrafish retain this capacity throughout their life, rodents can only regenerate injured myocardium during the first couple of days after birth. Clinical evidence also suggests that the human heart has some regenerative capacity at the time of birth. The exact mechanisms of cardiac regeneration and the postnatal loss of regenerative capacity of the heart are however unknown.