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Apoptosis in dilated cardiomyopathy
1Cardiology Division, Yonsei Cardiovascular Center, Yonsei University College of Medicine, Seoul, Korea.
Insights
Dilated cardiomyopathy (DCMP) involves myocyte loss, potentially due to apoptosis. This study confirms that programmed cell death, not necrosis or inflammation, is the primary mechanism for cell loss in DCMP.
Area of Science:
- Cardiovascular Pathology
- Cell Biology
- Molecular Cardiology
Background:
- Dilated cardiomyopathy (DCMP) presents with myocardial fibrosis and hypertrophy.
- Cellular degeneration, not necrosis, is observed in cardiac hypertrophy.
- The mechanism of myocyte loss in DCMP remains unclear.
Purpose of the Study:
- To investigate if apoptosis is the cause of myocyte loss in DCMP.
- To differentiate apoptosis from necrosis and inflammation in DCMP.
Main Methods:
- Endomyocardial biopsies from DCMP patients and controls were analyzed.
- Immunohistochemistry (TdT-mediated dUTP-biotin nick end-labeling) identified apoptosis.
- Confocal laser scanning microscopy confirmed apoptotic morphology.
Main Results:
- Apoptosis was extensively observed in myocytes (19.8-25.4% apoptotic index).
- Apoptosis was also detected in interstitial and vascular endothelial cells.
- Morphological analysis revealed characteristic condensed chromatin indicative of apoptosis.
Conclusions:
- Myocyte loss in DCMP is primarily caused by apoptosis.
- Apoptosis affects both myocytes and interstitial cells in DCMP.
- Inflammation and necrosis are not the main drivers of cell loss in DCMP.
Objective:
Cardiomyopathy, a popular diagnosis that always obscures more than it reveals, nevertheless has several characteristic histological features. These prominently include widespread focal myocardial fibrosis and associated hypertrophy of surviving cardiac myocyte. In fact, focal noninflammatory degeneration (not necrosis) has been demonstrated as a feature of many forms of cardiac hypertrophy. We hypothesized that this loss of myocardial cells in dilated cardiomyopathy (DCMP) may result from cell death by apoptosis.
Methods:
Endomyocardial biopsy specimens from the right ventricles of six patients who suffered from DCMP were studied, and myocardial specimens from two persons who died in motor vehicle accidents were used as negative controls. For identification of apoptosis, immunohistochemistry with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling was performed. In addition, apoptosis was confirmed morphologically by confocal laser scanning microscopy with propidium iodide.
Results:
Apoptosis, that was represented by an apoptotic index ranging from 19.8 to 25.4%, could be extensively seen in myocytes and also rarely in non-myocytes of interstitium and vascular endothelium. Morphologically, there were a lot of nuclei with clumps of condensed chromatin, suggestive of apoptosis.
Conclusion:
The present study demonstrated that myocyte loss in DCMP might be mainly due to the apoptosis of myocytes and interstitial cells, rather than inflammation or cell necrosis.