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Updated: Jun 21, 2026
In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model
Published on: October 27, 2020
Hibernating myocardium: Programmed cell survival or programmed cell death?
1Department of Molecular Cell Biology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
Insights
Cardiomyocyte dedifferentiation, a switch to a fetal phenotype, is observed in heart remodeling. Its role in cardiac pathology remains controversial, debated as either programmed cell survival or cell death.
Area of Science:
- Cardiovascular Biology
- Cellular Cardiology
- Cardiac Pathophysiology
Background:
- Programmed cell death (apoptosis) is a known cause of cardiomyocyte loss in myocardial infarction and cardiomyopathies.
- The role of cell death in conditions like hibernating or stunned myocardium is less clear.
- The heart undergoes stereotypical structural remodeling under stress, involving cardiomyocyte dedifferentiation.
Purpose of the Study:
- To explore the controversial role of cardiomyocyte dedifferentiation in cardiac pathology.
- To investigate whether dedifferentiation represents a survival or death pathway.
- To clarify the adaptive versus degenerative nature of the fetal phenotype switch.
Main Methods:
- Review of recent studies on cardiac remodeling and cardiomyocyte adaptation.
- Analysis of structural hallmarks of dedifferentiation in cardiomyocytes.
- Evaluation of evidence for adaptive and reversible dedifferentiation versus degenerative cell death.
Main Results:
- Cardiomyocytes dedifferentiate to a fetal phenotype under stress, characterized by reduced contractile filaments, glycogen accumulation, altered mitochondria, and loss of sarcoplasmic reticulum.
- This dedifferentiation involves changes in protein expression and organelle structure.
- Evidence suggests dedifferentiation may be adaptive and reversible ('programmed cell survival') or part of programmed cell death.
Conclusions:
- The interpretation of cardiomyocyte dedifferentiation as either a survival or death mechanism is a critical, unresolved issue.
- Resolving this controversy has direct clinical implications for cardiac disease prognosis and therapeutic strategies.
- Further research is needed to definitively classify cardiomyocyte dedifferentiation in cardiac pathologies.
Abstract:
Evidence that programmed cell death contributes to cardiomyocyte loss is substantial for some cardiac pathologies such as myocardial infarction and a variety of cardiomyopathies. For others, such as chronic hibernating and stunned myocardium, its involvement is still debated. Recent studies have indicated that the heart remodels its structure in a rather stereotypical way when subjected to unfavourable conditions such as ischemia and pressure or volume overload. This stereotypical response is characterized by subcellular adaptations in cardiomyocytes whereby the cells switch from an adult (functional) to a fetal (survival) phenotype, a process akin to dedifferentiation. Structural hallmarks of dedifferentiation are reduction of contractile filaments, accumulation of glycogen in the cytosol, dispersion of nuclear heterochromatin, changes in mitochondrial shape and size, and loss of sarcoplasmic reticulum and T-tubules. The changes are accompanied by important alterations in the expression and distribution of structural proteins in these organelles. Today, there is only circumstantial evidence that cardiomyocyte dedifferentiation is an adaptive and reversible phenomenon instead of a degenerative event leading to apoptotic cell death. Indeed, some research groups consider the switch to a fetal phenotype to be a rescue reaction and therefore coined the name 'programmed cell survival', whereas others interpret this as an event on the 'programmed cell death' pathway. It is obvious that resolving this controversial issue is of direct clinical importance as far as prognosis and therapy are concerned.
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