BACKGROUND: The precise molecular mechanism of Adriamycin-induced cardiomyopathy (ADR-CM) is still unknown. We address the demonstration of apoptotic myocardial cell death and the apoptosis-inducing molecules in ADR-CM induced in rats. METHODS AND RESULTS: Until 8 weeks after the first administration of ADR, there was no increase in the number of labeled cells by terminal deoxynucleotidyl transferase assay (TUNEL method). Apoptotic indices increased significantly at weeks 9 and 10 in hearts of the ADR-treated group but not in those of the control group (0.42+/-0.12% versus 0.10+/-0.02% and 0.86+/-0.11% versus 0.09+/-0.04% at weeks 9 and 10, respectively). DNA ladder formation was also observed in the myocardial tissues during the late stages of the ADR-CM of rats. There was no significant difference in expression of p53 gene between the ADR group and the control group at either the message or the protein level. An overexpression of Fas antigen was shown in myocardial cells of ADR-treated hearts at weeks 9 and 10 by both Western blotting and immunofluorescent staining. Furthermore, we confirmed that neutralization of anti-Fas ligand antibody inhibited ADR-induced apoptosis. CONCLUSIONS: Apoptotic cell death was observed in the hearts of ADR-CM rats, and the number of apoptotic myocardial cells increased with the deterioration of morphological findings and cardiac function, indicating that apoptosis may be an important mechanism of loss of myocardial cells and cardiac dysfunction in ADR-CM. Apoptosis in ADR-CM rats is not p53-dependent but rather is executed through a Fas-mediated pathway.
BACKGROUND: The precise molecular mechanism of Adriamycin-induced cardiomyopathy (ADR-CM) is still unknown. We address the demonstration of apoptotic myocardial cell death and the apoptosis-inducing molecules in ADR-CM induced in rats. METHODS AND RESULTS: Until 8 weeks after the first administration of ADR, there was no increase in the number of labeled cells by terminal deoxynucleotidyl transferase assay (TUNEL method). Apoptotic indices increased significantly at weeks 9 and 10 in hearts of the ADR-treated group but not in those of the control group (0.42+/-0.12% versus 0.10+/-0.02% and 0.86+/-0.11% versus 0.09+/-0.04% at weeks 9 and 10, respectively). DNA ladder formation was also observed in the myocardial tissues during the late stages of the ADR-CM of rats. There was no significant difference in expression of p53 gene between the ADR group and the control group at either the message or the protein level. An overexpression of Fas antigen was shown in myocardial cells of ADR-treated hearts at weeks 9 and 10 by both Western blotting and immunofluorescent staining. Furthermore, we confirmed that neutralization of anti-Fas ligand antibody inhibited ADR-induced apoptosis. CONCLUSIONS: Apoptotic cell death was observed in the hearts of ADR-CM rats, and the number of apoptotic myocardial cells increased with the deterioration of morphological findings and cardiac function, indicating that apoptosis may be an important mechanism of loss of myocardial cells and cardiac dysfunction in ADR-CM. Apoptosis in ADR-CM rats is not p53-dependent but rather is executed through a Fas-mediated pathway.
Authors: R Maruyama; G Takemura; T Aoyama; K Hayakawa; M Koda; Y Kawase; X Qiu; Y Ohno; S Minatoguchi; K Miyata; T Fujiwara; H Fujiwara Journal: Am J Pathol Date: 2001-08 Impact factor: 4.307
Authors: Christophe M M Lahorte; Jean-Luc Vanderheyden; Neil Steinmetz; Christophe Van de Wiele; Rudi A Dierckx; Guido Slegers Journal: Eur J Nucl Med Mol Imaging Date: 2004-05-12 Impact factor: 9.236
Authors: Chu Chang Chua; Jinping Gao; Ye-Shih Ho; Xingshun Xu; I-Chun Kuo; Kaw-Yan Chua; Hong Wang; Ronald C Hamdy; John C Reed; Balvin H L Chua Journal: Cardiovasc Res Date: 2008-09-18 Impact factor: 10.787