Myocardial DNA strand breaks are detected in biopsy tissues from patients with dilated cardiomyopathy

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.