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Histological assessment of apoptotic cell death in cardiomyopathies
N G Kavantzas1, A C Lazaris, E V Agapitos
1Department of Pathology, School of Medicine, National University of Athens, Greece. nkavan@cc.uoa.gr
Insights
Apoptosis, or programmed cell death, is elevated in hypertrophic cardiomyopathy and arrhythmogenic right ventricle dysplasia but not dilated cardiomyopathy. This finding suggests apoptosis plays a role in specific heart diseases.
Area of Science:
- Cardiology
- Cell Biology
- Pathology
Background:
- Apoptosis (programmed cell death) in the heart muscle (myocardium) is complex and challenging to detect.
- Myocyte apoptosis is typically scattered and affects individual cells within the myocardial wall.
Purpose of the Study:
- To quantify the extent of apoptosis in endomyocardial biopsies from patients with dilated cardiomyopathy, hypertrophic cardiomyopathy, and arrhythmogenic right ventricle dysplasia.
- To compare apoptosis levels in these conditions with those in healthy control subjects.
Main Methods:
- Utilized immunohistochemistry with the TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) method on paraffin-embedded myocardial sections.
- Calculated the TUNEL index, representing the percentage of TUNEL-positive nuclei out of 200 counted nuclei per specimen.
- Assessed cellular morphology alongside TUNEL staining to confirm apoptotic cell death.
Main Results:
- Mean TUNEL index was 4% for dilated cardiomyopathy, 17.5% for arrhythmogenic right ventricle dysplasia, and 18.5% for hypertrophic cardiomyopathy.
- No apoptotic myocardial cell death was detected in normal subjects (transplanted hearts).
- Significantly higher numbers of apoptotic cells were observed in hypertrophic cardiomyopathy and arrhythmogenic right ventricle dysplasia compared to dilated cardiomyopathy.
Conclusions:
- Apoptosis is a significant biological process in the development of certain heart diseases, including hypertrophic cardiomyopathy and arrhythmogenic right ventricle dysplasia.
- The specific role of apoptosis in the pathophysiology of these heart conditions requires further investigation.
- Apoptosis levels differ markedly between dilated cardiomyopathy and other cardiomyopathies studied.
Abstract:
Apoptosis in the myocardium is complex and often difficult to recognise. Myocyte apoptosis is scattered across the myocardial wall and is restricted to individual cells. In the present study, we describe the amount of apoptosis in 50 endomyocardial biopsies taken from 50 patients with dilated cardiomyopathy, in 14 hearts with hypertrophic cardiomyopathy and in five hearts with arrhythmogenic dysplasia of the right ventricle. As a control group, 15 endomyocardial biopsies from 15 transplanted hearts (of live patients) were used. Apoptosis was immunohistochemically determined in paraffin sections with the TUNEL method. In each specimen the TUNEL index was calculated as the percentage of TUNEL-positive nuclei among a total number of 200 counted nuclei. Cellular morphology was assessed in conjunction with TUNEL staining. The mean percentage of TUNEL-positive myocardial cells varied from 4% for dilated cardiomyopathy to 17.5% for arrhythmogenic right ventricle dysplasia and 18.5% for hypertrophic cardiomyopathy, whereas no signs of apoptotic myocardial cell death were found in normal subjects. The numbers of apoptotic cells in dilated cardiomyopathy specimens were significantly lower by comparison with both those of hypertrophic cardiomyopathy and those of arrhythmogenic right ventricular dysplasia specimens. It is evident that apoptosis constitutes a major biological phenomenon in the development of at least some heart diseases, but its role in their pathophysiology has yet to be delineated.