PURPOSE OF REVIEW: Congenital heart disease is the most common birth defect and acquired heart disease is the leading cause of death in adults. Understanding the mechanisms that drive cardiomyocyte proliferation and differentiation has the potential to advance the understanding and potentially the treatment of different cardiac pathologies, ranging from myopathies and heart failure to myocardial infarction. This review focuses on studies aimed at elucidating signal transduction pathways and molecular mechanisms that promote proliferation, differentiation, and regeneration of differentiated heart muscle cells, cardiomyocytes.

RECENT FINDINGS: There is now significant evidence that demonstrates cardiomyocytes continue to proliferate into adulthood. Potential regulators have been identified, including cell cycle regulators, extracellular ligands such as neuregulin, epigenetic targets, reactive oxygen species, and microRNA. The necessary steps should involve validating and applying the new knowledge about cardiomyocyte regeneration towards the development of therapeutic targets for patients. This will be facilitated by the application of standardized pre-clinical models to study cardiomyocyte regeneration.