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Myocyte cell death and ventricular remodeling
P Anversa1, G Olivetti, A Leri
1Department of Medicine, New York Medical College, Valhalla 10595, USA.
Abstract:
The recognition that cell death in the myocardium is not only necrotic in nature but is also mediated by activation of the suicide program of myocytes has raised several questions concerning the magnitude of this phenomenon, and whether these two distinct forms of cell death are disease-dependent or coexist in the pathologic heart. Additionally, the times required for the completion of apoptotic and necrotic myocyte cell death are unknown, making the analysis of their respective rates in the myocardium impossible at present. The documentation that mechanical forces in vitro, mimicking diastolic Laplace overloading in vivo, can transmit a death signal to myocytes suggests that programmed cell death may be triggered in the stressed myocardium independently from the etiology of the overload. Because increasing pressure or volume loads, or both, in the failing heart induce myocyte hypertrophy and proliferation, a challenging question is whether the induction of genes regulating these cellular growth processes may activate programmed cell death as well. Finally, the identification of the mechanisms responsible for the translation of a diffuse environmental condition into a death signal in a limited number of cells scattered across the ventricular wall is a major challenge of future research.
Insights
Myocyte cell death in the heart involves both necrosis and programmed cell death (apoptosis). Understanding their rates and triggers in stressed hearts is crucial for future research.
Area of Science:
- Cardiovascular Biology
- Cell Death Mechanisms
- Cardiac Pathophysiology
Background:
- Myocardial cell death is recognized to involve both necrosis and programmed cell death (apoptosis) in myocytes.
- The relative contribution and disease-dependency of these cell death pathways in pathological hearts remain unclear.
- The temporal dynamics of myocyte apoptosis and necrosis are not well-defined, hindering rate analysis.
Purpose of the Study:
- To explore the magnitude and interplay of necrotic and apoptotic myocyte cell death in the heart.
- To investigate whether mechanical forces and cellular growth processes can trigger programmed cell death in stressed myocardium.
- To identify the mechanisms underlying the initiation of myocyte death signals in response to environmental conditions.
Main Methods:
- Review and synthesis of existing literature on myocyte cell death pathways.
- Analysis of in vitro studies demonstrating mechanical force-induced myocyte death signals.
- Conceptual exploration of gene regulation in cardiac hypertrophy and its link to programmed cell death.
Main Results:
- Mechanical forces mimicking diastolic Laplace overloading can transmit death signals to myocytes in vitro.
- Programmed cell death may be triggered in stressed myocardium irrespective of the overload's etiology.
- A key challenge is understanding how cellular growth induction in failing hearts might activate programmed cell death.
Conclusions:
- Further research is needed to determine the rates and disease-dependency of myocyte necrosis versus apoptosis.
- Mechanical stress and cellular growth signaling are potential triggers for programmed myocyte death.
- Elucidating the mechanisms translating environmental conditions into localized myocyte death signals is a critical future research direction.