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Updated: Jul 25, 2025
Simultaneous Assessment of Cardiomyocyte DNA Synthesis and Ploidy: A Method to Assist Quantification of Cardiomyocyte Regeneration and Turnover
Published on: May 23, 2016
Cardiomyocyte Ploidy, Metabolic Reprogramming and Heart Repair
Andrea Elia1, Sadia Mohsin2, Mohsin Khan1,3
1Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.
Insights
Heart muscle cells (cardiomyocytes) normally cannot divide. Metabolic changes influence cardiomyocyte division and regeneration after heart injury, offering new therapeutic avenues.
Area of Science:
- Cardiovascular Biology
- Cellular Metabolism
- Regenerative Medicine
Background:
- Adult cardiomyocytes (CMs) are terminally differentiated and lack regenerative capacity after myocardial injury.
- Developing CMs are proliferative and contribute to cardiac tissue regeneration.
- CM maturation involves polyploidization and binucleation, altering function and metabolism.
Purpose of the Study:
- To review changes in cardiomyocyte ploidy and nucleation during cardiac development, maturation, and injury.
- To explore the role of metabolic reprogramming in CM cell cycle reentry and fate transitions.
- To discuss the impact of metabolism on CM proliferation and cardiac regeneration.
Main Methods:
- Literature review of studies on cardiomyocyte development, maturation, and response to injury.
- Analysis of research on metabolic changes associated with CM ploidy and nucleation.
- Synthesis of findings on the link between metabolism, cell cycle, and cardiac regeneration.
Main Results:
- CMs transition from mononucleated diploid to polyploid/binucleated states during maturation.
- Metabolic reprogramming is crucial for CM cell cycle reentry and ploidy changes.
- These metabolic and cellular changes enhance cardiac structure and function post-injury.
Conclusions:
- Metabolism significantly influences cardiomyocyte fate, including mononucleation/binucleation and cell cycle progression.
- Understanding these metabolic-cardiomyocyte interactions is key to promoting cardiac regeneration.
- Targeting metabolic pathways may offer novel strategies for treating heart disease.
Abstract:
The adult heart is made up of cardiomyocytes (CMs) that maintain pump function but are unable to divide and form new myocytes in response to myocardial injury. In contrast, the developmental cardiac tissue is made up of proliferative CMs that regenerate injured myocardium. In mammals, CMs during development are diploid and mononucleated. In response to cardiac maturation, CMs undergo polyploidization and binucleation associated with CM functional changes. The transition from mononucleation to binucleation coincides with unique metabolic changes and shift in energy generation. Recent studies provide evidence that metabolic reprogramming promotes CM cell cycle reentry and changes in ploidy and nucleation state in the heart that together enhances cardiac structure and function after injury. This review summarizes current literature regarding changes in CM ploidy and nucleation during development, maturation and in response to cardiac injury. Importantly, how metabolism affects CM fate transition between mononucleation and binucleation and its impact on cell cycle progression, proliferation and ability to regenerate the heart will be discussed.
