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Updated: May 3, 2026
Acute Myocardial Infarction in Rats
Published on: February 17, 2011
Fas-mediated apoptosis in adriamycin-induced cardiomyopathy in rats: In vivo study
1Department of Pediatrics, Kanazawa Medical University, Ishikawa, Japan.
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.
Insights
Adriamycin-induced cardiomyopathy (ADR-CM) involves apoptotic myocardial cell death. This cell death is mediated by the Fas pathway, not the p53 gene, in rats.
Area of Science:
- Cardiology
- Molecular Biology
- Toxicology
Background:
- The molecular mechanisms underlying Adriamycin-induced cardiomyopathy (ADR-CM) remain unclear.
- This study investigates apoptotic myocardial cell death and its molecular mediators in a rat model of ADR-CM.
Purpose of the Study:
- To elucidate the role of apoptosis in Adriamycin-induced cardiomyopathy.
- To identify the specific molecular pathways involved in ADR-CM-related myocardial cell death.
Main Methods:
- Terminal deoxynucleotidyl transferase assay (TUNEL) to detect apoptosis.
- Western blotting and immunofluorescent staining to assess protein expression (p53 and Fas antigen).
- Administration of anti-Fas ligand antibody to neutralize Fas-mediated apoptosis.
Main Results:
- Apoptotic indices significantly increased at weeks 9 and 10 post-Adriamycin administration.
- DNA ladder formation confirmed apoptosis in late-stage ADR-CM.
- Fas antigen overexpression was observed in myocardial cells, while p53 expression remained unchanged.
- Neutralization of Fas ligand inhibited Adriamycin-induced apoptosis.
Conclusions:
- Apoptotic cell death is a key mechanism contributing to myocardial cell loss and cardiac dysfunction in ADR-CM.
- The observed apoptosis in ADR-CM is independent of the p53 pathway.
- Apoptosis in ADR-CM is primarily executed through a Fas-mediated pathway.
