Mechanisms of Cardiomyocyte Proliferation and Differentiation in Development and Regeneration
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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.
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.
KeywordsCardiomyocyte Proliferation Differentiation Regeneration Cell cycle
This research was supported by the Richard King Mellon Foundation Institute for Pediatric Research (Children’s Hospital of Pittsburgh of UPMC), by a Transatlantic Network of Excellence grant by Fondation Leducq (15CVD03), Children’s Cardiomyopathy Foundation, and NIH grants R01HL106302 and U01MH098953 (to BK). We apologize for the researchers whose publications we were not able to discuss and cite due to space constraints.
Compliance with Ethical Standards
Conflict of Interest
Jessie Wettig Yester and Bernhard Kühn declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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