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Apoptosis in myocytes in end-stage heart failure
J Narula1, N Haider, R Virmani
1Massachusetts General Hospital and Harvard Medical School, Boston 02115, USA.
Insights
Myocyte loss through apoptosis (programmed cell death) is evident in end-stage cardiomyopathy, potentially driving progressive heart failure. This study investigated apoptosis in explanted hearts, finding significant evidence in dilated cardiomyopathy.
Area of Science:
- Cardiology
- Cell Biology
- Pathology
Background:
- Heart failure stems from diverse causes like ischemic and hypertensive heart disease.
- Cellular mechanisms behind heart failure's myocardial dysfunction are not fully understood.
- Apoptosis (programmed cell death) is a potential contributor to heart failure progression.
Purpose of the Study:
- To investigate the presence and extent of apoptosis in explanted human hearts from patients with end-stage cardiomyopathy.
- To determine if apoptosis contributes to myocardial dysfunction in dilated and ischemic cardiomyopathy.
Main Methods:
- Examined seven explanted hearts from patients with severe chronic heart failure (dilated and ischemic cardiomyopathy).
- Utilized in situ end-labeling and agarose-gel electrophoresis to detect DNA fragmentation, a marker of apoptosis.
- Employed myocardial tissues from recent myocardial infarction and healthy individuals as positive and negative controls, respectively.
Main Results:
- Histochemical evidence of DNA fragmentation, indicative of apoptosis, was found in all four hearts with idiopathic dilated cardiomyopathy and one of three with ischemic cardiomyopathy.
- DNA laddering, a hallmark of apoptosis, was present in all dilated cardiomyopathy samples but absent in ischemic cardiomyopathy samples.
- Apoptosis was observed in acute myocardial infarcts but not in remote myocardium; rare apoptotic myocytes were found in control tissues.
Conclusions:
- Myocyte loss via apoptosis is a significant feature in end-stage cardiomyopathy.
- Apoptosis may play a crucial role in the progressive myocardial dysfunction characteristic of heart failure.
Background:
Heart failure can result from a variety of causes, including ischemic, hypertensive, toxic, and inflammatory heart disease. However, the cellular mechanisms responsible for the progressive deterioration of myocardial function observed in heart failure remain unclear and may result from apoptosis (programmed cell death).
Methods:
We examined seven explanted hearts obtained during cardiac transplantation for evidence of apoptosis. All seven patients had severe chronic heart failure: four had idiopathic dilated cardiomyopathy, and three had ischemic cardiomyopathy. DNA fragmentation (an indicator of apoptosis) was identified histochemically by in situ end-labeling as well as by agarose-gel electrophoresis of end-labeled DNA. Myocardial tissues obtained from four patients who had had a myocardial infarction one to two days previously were used as positive controls, and heart tissues obtained from four persons who died in motor vehicle accidents were used as negative controls for the end-labeling studies.
Results:
Hearts from all four patients with idiopathic dilated cardiomyopathy and from one of the three patients with ischemic cardiomyopathy had histochemical evidence of DNA fragmentation. All four myocardial samples from patients with dilated cardiomyopathy also demonstrated DNA laddering, a characteristic of apoptosis, whereas this was not seen in any of the samples from patients with ischemic cardiomyopathy. Histological evidence of apoptosis was also observed in the central necrotic zone of acute myocardial infarcts, but not in myocardium remote from the infarcted zone. Rare isolated apoptotic myocytes were seen in the myocardium from the four persons who died in motor vehicle accidents.
Conclusions:
Loss of myocytes due to apoptosis occurs in patients with end-stage cardiomyopathy and may contribute to progressive myocardial dysfunction.