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Myocardial DNA strand breaks are detected in biopsy tissues from patients with dilated cardiomyopathy
1Third Department of Internal Medicine, Kurume University School of Medicine, Japan.
Insights
DNA strand breaks were found in heart cells of patients with dilated cardiomyopathy (DCM) and myocarditis. This suggests a role for apoptosis in the progressive loss of heart function in these conditions.
Area of Science:
- Cardiology
- Cell Biology
- Pathology
Background:
- Dilated cardiomyopathy (DCM) involves cardiomyocyte damage and fibrosis, with minimal inflammation, suggesting non-necrotic cell death mechanisms.
- Understanding the precise mechanisms of cardiomyocyte loss in DCM and myocarditis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the potential role of apoptosis in the pathogenesis of dilated cardiomyopathy (DCM) and myocarditis.
- To assess the presence of DNA strand breaks, a marker of apoptosis, in myocardial tissue from patients with DCM and myocarditis.
Main Methods:
- Endomyocardial biopsies were obtained from patients with DCM (n=9), myocarditis (n=4), and controls (n=5).
- The TUNEL assay was employed for in situ detection of DNA strand breaks (oligonucleosomal DNA fragmentation).
- Electron microscopy was used to examine cellular morphology for features of apoptosis.
Main Results:
- TUNEL-positive cells, indicating DNA strand breaks, were detected in 3/9 DCM patients and all 4 myocarditis patients, but not in controls.
- In DCM, TUNEL-positive nuclei were exclusively in cardiomyocytes, while in myocarditis, they were primarily in interstitial cells.
- Increased interstitial fibrosis was observed in TUNEL-positive DCM patients compared to TUNEL-negative ones (p < 0.05).
- Electron microscopy did not reveal definitive morphologic signs of cardiomyocyte apoptosis in either DCM or myocarditis.
Conclusions:
- DNA strand breaks were identified in cardiomyocytes in DCM and predominantly in interstitial cells in myocarditis.
- These findings suggest that DNA strand breaks may contribute to the progressive loss of functional cardiac units in DCM and myocarditis.
- While TUNEL assay indicates DNA damage, definitive apoptotic morphology was not observed, warranting further investigation into the specific cell death pathways involved.
Background:
Progressive damage of cardiomyocytes with interstitial and replacement fibrosis accompanied by less inflammatory cell infiltration is observed in patients with dilated cardiomyopathy (DCM), suggesting some other mechanisms rather than necrotic cell death.
Hypothesis:
The aim of this study was to assess the possible involvement of apoptotic process in the pathogenesis of DCM and myocarditis.
Methods:
Endomyocardial biopsy was performed in patients with DCM (n = 9), myocarditis (n = 4), or atypical chest pain syndrome (as controls; n = 5). The TUNEL method was used for in situ detection of oligonucleosomal DNA strand breaks.
Results:
The TUNEL-positive cells were observed in three of nine patients with DCM and in all four with myocarditis, but in none of the controls. The TUNEL-positive nuclei were observed exclusively in cardiomyocytes in DCM, whereas in myocarditis they were detected mainly in interstitial cells and in a few myocytes. In DCM, interstitial fibrosis was greater in the TUNEL-positive than in TUNEL-negative patients (p < 0.05). In either DCM or myocarditis, electron microscopic examination could not reveal morphologic features of apoptosis of cardiomyocytes.
Conclusion:
The DNA strand breaks were detected in cardiomyocytes in patients with DCM and mainly in interstitial cells in myocarditis. It is possible that the DNA strand breaks can be involved in mechanisms of progressive loss of functional cardiac units in these myocardial diseases.