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Updated: Jul 14, 2026
Analysis of Cardiomyocyte Development using Immunofluorescence in Embryonic Mouse Heart
Published on: March 26, 2015
Cyclin-dependent kinase inhibitor expression in human heart failure. A comparison with fetal development
P B Burton1, M H Yacoub, P J Barton
1Imperial College of School of Medicine, National Heart and Lung Institute, London, U.K.
Aims:
Terminal differentiation of cardiac myocyte is associated with their permanent withdrawal from the cell cycle. In adult end-stage heart failure, significant numbers of myocytes express proliferating cell nuclear antigen yet fail to progress to cell division. Cyclin dependent kinase inhibitors are powerful inhibitors of the cell cycle and may play a direct role both in myocyte development and in preventing cell division in the adult.
Methods And Results:
The expression of the CIP/KIP cyclin dependent kinase inhibitors p21, p27, p57 and the retinoblastoma protein was examined in acute (seen in brain dead transplant donors) and end-stage heart failure by Western blot analysis and compared to that seen in human and rat cardiac development. The expression of p21 showed a gradual increase during development in both rat and man, becoming maximal in adulthood p27. levels showed an initial rise with subsequent continual expression throughout life. p57 expression was detectable at only early stages in rat but persisted throughout life in man. In both acute and end-stage heart failure the levels of p21, p27 and p57 reverted to a pattern similar to that observed in human fetal heart: p21 and p27 declined while p57 expression was significantly increased. In contrast, retinoblast protein levels declined during human heart development but were unaltered in heart failure.
Conclusions:
The expression of p21, but not p27 or p57, is consistent with a role in the gradual withdrawal of cardiac myocytes from cell cycle during development. In adult heart failure cyclin dependent kinase inhibitor expression reverts to the fetal pattern but is insufficient to initiate cell cycle activation.
Insights
In heart failure, cell cycle inhibitors like p21 revert to fetal patterns, hindering cardiac myocyte division. This suggests these inhibitors play a role in myocyte development and preventing cell division in adults.
Area of Science:
- Cardiovascular Biology
- Cell Cycle Regulation
- Molecular Cardiology
Background:
- Cardiac myocyte terminal differentiation involves permanent cell cycle withdrawal.
- Adult heart failure shows myocytes expressing proliferation markers but failing to divide.
- Cyclin-dependent kinase inhibitors (CKIs) are key regulators of cell cycle progression.
Purpose of the Study:
- To investigate the expression patterns of CKIs (p21, p27, p57) and retinoblastoma protein during cardiac development and in heart failure.
- To determine the role of CKIs in the cell cycle exit of cardiac myocytes.
Main Methods:
- Western blot analysis was used to examine protein expression levels.
- Expression of p21, p27, p57, and retinoblastoma protein was analyzed in developing rat and human hearts.
- Protein levels were also assessed in acute and end-stage human heart failure samples.
Main Results:
- During development, p21 expression increased, p27 showed initial rise then sustained levels, and p57 persisted in humans.
- In heart failure, p21 and p27 levels decreased, while p57 increased, resembling fetal patterns.
- Retinoblastoma protein levels decreased during development but remained unchanged in heart failure.
Conclusions:
- p21 expression correlates with cardiac myocyte withdrawal from the cell cycle during development.
- In adult heart failure, CKI expression shifts to a fetal-like pattern.
- This altered CKI expression is insufficient to induce cell cycle re-activation in failing adult myocytes.
