Excessive Antioxidant Activity Impedes Neonatal Cardiomyocyte Regeneration
Significance Heart disease accounts for 1 in 4 deaths in the United States annually, making it one of the leading causes of death and related morbidity resents a significant economic burden. Mammalian cardiomyocytes are terminally differentiated with low turnover rate, insufficient to repopulate myocardium after heart attack caused by myocardial infarction (MI). As such, there is an urgent need for the development of non-invasive, effective, and efficient therapeutic approaches for treating MI. One strategy is to promote proliferation in mature cardiomyocytes, inspired by the observation of a transient regenerative window in neonatal mouse cardiomyocytes. During postnatal development, it is believed that cardiomyocytes exit cell cycle in response to high oxygen environment and a metabolic shift to oxidative phosphorylation. Strategies to lower oxidative stress in neonatal mouse hearts to prolong regenerative time window have been reported. While many studies have focused on mitigating injury-related ROS, it is not clear whether the developmental ROS increase in neonatal cardiomyocytes plays a role during postnatal myocardial maturation and establishment of injury response. The following study details the crucial role of neonatal ROS as signaling molecules in cardiomyocyte injury response after MI. Overall design: Mouse pups were treated with N-acetylcysteine (NAC) or saline P0-P1 before MI or sham surgery at P2. At P3, cardiomyocytes were isolated by enzymatic digestion of pooled whole ventricular tissue followed by selection via a neonatal cardiomyocyte isolation kit.  Three replicates were included per group to understand the transcriptomic differences of NAC treat in an uninjured and injured state.