The Neonatal Myeloid Hypoxia Response Promotes a Cardiac Regenerative Response through Insulin-Like Growth Factor

Background: The adult mammalian heart lacks the regenerative potential required to replenish depleted cardiomyocytes and restore cardiac function after injury. Ischemic cardiac injury contributes to heart failure, a leading cause of death worldwide. Neonatal mice possess the capacity to regenerate injured myocardium and macrophages contribute to this process. The mechanisms contributing to the regenerative crosstalk between macrophages and cardiomyocytes remain incompletely elucidated and offer potential to inform future therapeutic strategies. Methods: ) and reconstituting HIF-dependent mitogens. In parallel, we examined epigenetic and transcriptional signatures of the cardiac macrophage response and focused on intercellular crosstalk with cardiomyocytes. Results: . Parallel multiomic analysis revealed epigenetic regenerative signatures. Conclusions: in neonatal cardiac regeneration, likely through IGF-1 signaling.