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Updated: Jul 16, 2026
Isolation, Culture and Transduction of Adult Mouse Cardiomyocytes
Published on: August 28, 2016
Targeted expression of cyclin D2 results in cardiomyocyte DNA synthesis and infarct regression in transgenic mice
Kishore B S Pasumarthi1, Hidehiro Nakajima, Hisako O Nakajima
1Wells Center for Pediatric Research and Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Ind 46202-5225, USA.
Abstract:
Restriction point transit and commitment to a new round of cell division is regulated by the activity of cyclin-dependent kinase 4 and its obligate activating partners, the D-type cyclins. In this study, we examined the ability of D-type cyclins to promote cardiomyocyte cell cycle activity. Adult transgenic mice expressing cyclin D1, D2, or D3 under the regulation of the alpha cardiac myosin heavy chain promoter exhibited high rates of cardiomyocyte DNA synthesis under baseline conditions. Cardiac injury in mice expressing cyclin D1 or D3 resulted in cytoplasmic cyclin D accumulation, with a concomitant reduction in the level of cardiomyocyte DNA synthesis. In contrast, cardiac injury in mice expressing cyclin D2 did not alter subcellular cyclin localization. Consequently, cardiomyocyte cell cycle activity persisted in injured hearts expressing cyclin D2, ultimately resulting in infarct regression. These data suggested that modulation of D-type cyclins could be exploited to promote regenerative growth in injured hearts.
Insights
Cyclin D2 promotes cardiomyocyte cell cycle activity and infarct regression after cardiac injury. This suggests D-type cyclins can be modulated for heart regeneration.
Area of Science:
- Cardiovascular Biology
- Cell Cycle Regulation
- Molecular Cardiology
Background:
- Cell cycle progression is tightly regulated by cyclin-dependent kinases (CDKs) and cyclins.
- D-type cyclins (cyclin D1, D2, D3) are key regulators of the restriction point, controlling cell division commitment.
- Cardiomyocytes typically exit the cell cycle post-mitosis, limiting heart regeneration capacity.
Purpose of the Study:
- To investigate the role of D-type cyclins in promoting cardiomyocyte cell cycle activity.
- To determine if D-type cyclins can enhance cardiac regeneration following injury.
Main Methods:
- Generation of adult transgenic mice expressing cardiac-specific cyclin D1, D2, or D3.
- Assessment of cardiomyocyte DNA synthesis under baseline and post-cardiac injury conditions.
- Analysis of cyclin D subcellular localization in response to cardiac injury.
Main Results:
- Transgenic expression of cyclin D1, D2, or D3 increased cardiomyocyte DNA synthesis at baseline.
- Cardiac injury led to cytoplasmic accumulation of cyclin D1/D3, reducing DNA synthesis.
- Cardiac injury in cyclin D2-expressing mice did not alter cyclin localization, preserving cardiomyocyte cell cycle activity and promoting infarct regression.
Conclusions:
- Cyclin D2, unlike D1 and D3, maintains cardiomyocyte cell cycle activity post-injury.
- Persistent cell cycle activity driven by cyclin D2 facilitates infarct regression and suggests a regenerative potential.
- Targeting D-type cyclins, particularly cyclin D2, may offer a therapeutic strategy for promoting heart regeneration.
