Apoptosis and proliferation of cardiomyocytes in heart failure of different etiologies.
Apoptosis and proliferation of myocytes were studied in human heart failure (HF). Endomyocardial samples from the right ventricle of 38 patients with terminal HF were compared with 10 traffic accident victims without a history of cardiovascular disease. The TUNEL method was used for the detection of apoptosis, and immunohistochemical methods were used for the evaluation of p53, bcl-2, proliferation cell nuclear antigen (PCNA), and proliferation marker MIB-1. Apoptosis of cardiomyocytes, which was not p53-dependent, was present in 0.07 % of myocytes in HF, whereas no apoptotic myocytes were found in the control group (p < 0.01). An increased expression of bcl-2 was found in HF compared to controls (p < 0.01), yet bcl-2 failed to protect myocytes from apoptosis. Increased expression of proliferation markers was found in myocytes in HF compared to controls (PCNA labeling: 3.7% vs. 1.2%, p < 0.01; MIB-1 labeling: 0.1% vs. 0%, p< 0.01). Nevertheless, no mitotic figures in cardiomyocytes were found in our specimens. The volume density of interstitium was 22% in HF vs. 10% in the control group (p < 0.01). In conclusion, apoptosis of cardiomyocytes and fibrosis play an important role in HF, whereas clinical importance and the rate of myocyte proliferation remain to be determined.
Petrovic
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D
Institute of Histology and Embryology, Medical Faculty of Ljubljana, University of Ljubljana, Ljubljana, Slovenia. daniel.petrovic@mf.uni-lj.si
Zorc-Pleskovic
R
R
Zorc
M
M
D000328:Adult; D034961:Antigens, Nuclear; D017209:Apoptosis; D002455:Cell Division; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D034961:Antigens, Nuclear; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53