The role of hormones and neurons in cardiomyocyte maturation

The heart undergoes profound morphological and functional changes as it continues to mature postnatally. However, this phase of cardiac development remains understudied. More recently, cardiac maturation research has attracted a lot of interest due to the need for more mature stem cell-derived cardiomyocytes for disease modeling, drug screening and heart regeneration. Additionally, neonatal heart injury models have been utilized to study heart regeneration, and factors regulating postnatal heart development have been associated with adult cardiac disease. Critical components of cardiac maturation are systemic and local biochemical cues. Specifically, cardiac innervation and the concentration of various metabolic hormones appear to increase perinatally and they have striking effects on cardiomyocytes. Here, we first report some of the key parameters of mature cardiomyocytes and then discuss the specific effects of neurons and hormonal cues on cardiomyocyte maturation. We focus primarily on the structural, electrophysiologic, metabolic, hypertrophic and hyperplastic effects of each factor. This review highlights the significance of underappreciated regulators of cardiac maturation and underscores the need for further research in this exciting field.