Heart failure is one of the most devastating diseases known to man, with mortality rates worse than many malignancies and a substantial burden of morbidity and health care costs. The pathophysiological basis of systolic heart failure is the inability of the adult heart to replace lost or damaged myocardium and, although limited myocyte turnover does occur in the adult heart, it is insufficient for restoration of contractile function. In this Leducq Network, we will investigate how oxidative events regulate cardiomyocyte proliferative activity. Our central hypothesis is that the redox state of cardiomyocytes regulates the endogenous regenerative capacity of the adult mammalian heart. The understanding of this pathway will open the door to new therapies based on the stimulation of cardiac regeneration.