Apoptosis of cardiomyocytes in myocarditis.
Apoptosis of cardiomyocytes has been reported to be involved in the pathogenesis of heart failure of different aetiologies. The purpose of this study is to assess the role and extent of apoptosis of cardiomyocytes in active myocarditis. Endomyocardial samples from the right ventricle of 22 patients with active myocarditis were compared with 25 traffic accident victims without a history of cardiovascular disease. Twenty-two patients fulfilled the histopathologic Dallas criteria for myocarditis. The TUNEL method and immunostaining for active caspase 3 were used for the detection of apoptosis. Immunohistochemical methods were used for the evaluation of regulators of apoptosis (p53, Bcl-2) and evaluation of interstitial cells (macrophages, T and B lymphocytes). Apoptosis of cardiomyocytes (TUNEL-positive and anti-caspase 3-positive cardiomyocytes), which was not p53-dependent, was present in 0.3 to 0.4% (0.3% by TUNEL method and 0.4% by immunostaining for active caspase 3) of cardiomyocytes in active myocarditis, whereas only few apoptotic cardiomyocytes (0.0006 +/- 0.002% TUNEL-positive cardiomyocytes and 0.001 +/- 0.002% active caspase 3-positive cardiomyocytes) were found in the control group (P = 0.001). Apoptotic (TUNEL-positive and active caspase 3-positive) cardiomyocytes were found in small clusters. An increased expression of Bcl-2 was found in active myocarditis compared to the controls (P < 0.01), yet Bcl-2 failed to protect myocytes from apoptosis. We provide evidence of apoptosis of cardiomyocytes in active myocarditis, which may be involved in the development of heart failure.
Zorc-Pleskovic
R
R
Institute of Histology and Embryology, Medical Faculty, University Ljubljana, Ljubljana, Slovenia.
Alibegović
A
A
Zorc
M
M
Milutinović
A
A
Radovanović
N
N
Petrović
D
D
D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009205:Myocarditis / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000737:chemistry* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; C505407:CASP3 protein, human; D053148:Caspase 3