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Updated: Jul 5, 2025
Transthoracic Echocardiographic Examination in the Rabbit Model
Published on: June 1, 2019
Cardiac miRNA expression during the development of chronic anthracycline-induced cardiomyopathy using an experimental
Michaela Adamcova1, Helena Parova2, Olga Lencova-Popelova3
1Department of Physiology, Hradec Kralove, Czechia.
Abstract:
Background: Anthracycline cardiotoxicity is a well-known complication of cancer treatment, and miRNAs have emerged as a key driver in the pathogenesis of cardiovascular diseases. This study aimed to investigate the expression of miRNAs in the myocardium in early and late stages of chronic anthracycline induced cardiotoxicity to determine whether this expression is associated with the severity of cardiac damage. Method: Cardiotoxicity was induced in rabbits via daunorubicin administration (daunorubicin, 3 mg/kg/week; for five and 10 weeks), while the control group received saline solution. Myocardial miRNA expression was first screened using TaqMan Advanced miRNA microfluidic card assays, after which 32 miRNAs were selected for targeted analysis using qRT-PCR. Results: The first subclinical signs of cardiotoxicity (significant increase in plasma cardiac troponin T) were observed after 5 weeks of daunorubicin treatment. At this time point, 10 miRNAs (including members of the miRNA-34 and 21 families) showed significant upregulation relative to the control group, with the most intense change observed for miRNA-1298-5p (29-fold change, p < 0.01). After 10 weeks of daunorubicin treatment, when a further rise in cTnT was accompanied by significant left ventricle systolic dysfunction, only miR-504-5p was significantly (p < 0.01) downregulated, whereas 10 miRNAs were significantly upregulated relative to the control group; at this time-point, the most intense change was observed for miR-34a-5p (76-fold change). Strong correlations were found between the expression of multiple miRNAs (including miR-34 and mir-21 family and miR-1298-5p) and quantitative indices of toxic damage in both the early and late phases of cardiotoxicity development. Furthermore, plasma levels of miR-34a-5p were strongly correlated with the myocardial expression of this miRNA. Conclusion: To the best of our knowledge, this is the first study that describes alterations in miRNA expression in the myocardium during the transition from subclinical, ANT-induced cardiotoxicity to an overt cardiotoxic phenotype; we also revealed how these changes in miRNA expression are strongly correlated with quantitative markers of cardiotoxicity.
Insights
This study reveals that changes in microRNA (miRNA) expression in heart muscle are linked to anthracycline-induced cardiotoxicity. These miRNA alterations correlate with the severity of cardiac damage in early and late stages of treatment.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Oncology Therapeutics
Background:
- Anthracycline chemotherapy can cause cardiotoxicity, a significant complication in cancer treatment.
- MicroRNAs (miRNAs) play a crucial role in the development of cardiovascular diseases.
- Understanding miRNA expression in cardiotoxicity is vital for managing treatment side effects.
Purpose of the Study:
- To investigate myocardial miRNA expression during early and late stages of chronic anthracycline-induced cardiotoxicity.
- To determine the association between miRNA expression levels and the severity of cardiac damage.
- To identify specific miRNAs that serve as biomarkers for anthracycline cardiotoxicity.
Main Methods:
- Cardiotoxicity was induced in rabbits using daunorubicin (3 mg/kg/week for 5 and 10 weeks).
- Myocardial miRNA expression was screened using TaqMan Advanced miRNA assays.
- Quantitative real-time PCR (qRT-PCR) was used for targeted analysis of 32 selected miRNAs.
Main Results:
- Subclinical cardiotoxicity signs (elevated cardiac troponin T) appeared after 5 weeks, with 10 upregulated miRNAs, including miRNA-34 and miRNA-21 families (e.g., miR-1298-5p).
- After 10 weeks, significant left ventricle systolic dysfunction was observed, with 10 upregulated and one downregulated miRNA (miR-504-5p), notably miR-34a-5p (76-fold change).
- Strong correlations were found between multiple miRNAs (e.g., miR-34, miR-21, miR-1298-5p) and cardiotoxicity markers, including plasma miR-34a-5p levels.
Conclusions:
- This is the first study detailing miRNA expression changes during the progression from subclinical to overt anthracycline-induced cardiotoxicity.
- Alterations in myocardial miRNA expression are strongly correlated with quantitative markers of cardiotoxicity.
- Specific miRNAs may serve as early indicators and correlates of anthracycline-induced cardiac damage.
