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Updated: Aug 24, 2026

Visualization of Cell Cycle Variations and Determination of Nucleation in Postnatal Cardiomyocytes
Published on: February 24, 2017
Cyclin A2 mediates cardiomyocyte mitosis in the postmitotic myocardium
Hina W Chaudhry1, Nurin H Dashoush, Haiying Tang
1Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. hwc7@columbia.edu
Abstract:
Cell cycle withdrawal limits proliferation of adult mammalian cardiomyocytes. Therefore, the concept of stimulating myocyte mitotic divisions has dramatic implications for cardiomyocyte regeneration and hence, cardiovascular disease. Previous reports describing manipulation of cell cycle proteins have not shown induction of cardiomyocyte mitosis after birth. We now report that cyclin A2, normally silenced in the postnatal heart, induces cardiac enlargement because of cardiomyocyte hyperplasia when constitutively expressed from embryonic day 8 into adulthood. Cardiomyocyte hyperplasia during adulthood was coupled with an increase in cardiomyocyte mitosis, noted in transgenic hearts at all time points examined, particularly during postnatal development. Several stages of mitosis were observed within cardiomyocytes and correlated with the nuclear localization of cyclin A2. Magnetic resonance analysis confirmed cardiac enlargement. These results reveal a previously unrecognized critical role for cyclin A2 in mediating cardiomyocyte mitosis, a role that may significantly impact upon clinical treatment of damaged myocardium.
Insights
Cyclin A2 re-expression in adult hearts triggers cardiomyocyte cell division, leading to cardiac enlargement. This finding offers new avenues for treating cardiovascular disease through cardiomyocyte regeneration.
Area of Science:
- Cardiovascular Science
- Cell Biology
- Regenerative Medicine
Background:
- Adult mammalian cardiomyocytes normally withdraw from the cell cycle, limiting their proliferative capacity.
- Stimulating cardiomyocyte division is crucial for cardiac regeneration and treating cardiovascular diseases.
- Previous attempts to induce cardiomyocyte mitosis postnatally using cell cycle proteins have been unsuccessful.
Purpose of the Study:
- To investigate the role of cyclin A2 in cardiomyocyte proliferation and regeneration.
- To determine if forced expression of cyclin A2 can induce cardiomyocyte mitosis in postnatal hearts.
Main Methods:
- Constitutive expression of cyclin A2 in transgenic mice from embryonic day 8 into adulthood.
- Analysis of cardiomyocyte hyperplasia and mitosis at various time points.
- Magnetic resonance imaging to assess cardiac enlargement.
Main Results:
- Constitutive cyclin A2 expression induced cardiac enlargement due to cardiomyocyte hyperplasia.
- Increased cardiomyocyte mitosis was observed in transgenic hearts, particularly during postnatal development.
- Mitotic stages correlated with nuclear localization of cyclin A2.
Conclusions:
- Cyclin A2 plays a critical, previously unrecognized role in mediating cardiomyocyte mitosis.
- Reactivating cyclin A2 in postnatal cardiomyocytes can induce proliferation.
- This discovery holds significant potential for clinical strategies aimed at myocardial repair.
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