Cardiac miRNA expression during the development of chronic anthracycline-induced cardiomyopathy using an experimental rabbit model
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 anthracycl...
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1298172/full |
| _version_ | 1797367795628900352 |
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| author | Michaela Adamcova Helena Parova Olga Lencova-Popelova Petra Kollarova-Brazdova Ivana Baranova Marcela Slavickova Tereza Stverakova Petra Sauer Mikyskova Yvona Mazurova Martin Sterba |
| author_facet | Michaela Adamcova Helena Parova Olga Lencova-Popelova Petra Kollarova-Brazdova Ivana Baranova Marcela Slavickova Tereza Stverakova Petra Sauer Mikyskova Yvona Mazurova Martin Sterba |
| author_sort | Michaela Adamcova |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T17:23:16Z |
| format | Article |
| id | doaj.art-f83ce078741d4dc8bffe8e0185a65413 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-08T17:23:16Z |
| publishDate | 2024-01-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-f83ce078741d4dc8bffe8e0185a654132024-01-03T04:21:00ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-01-011410.3389/fphar.2023.12981721298172Cardiac miRNA expression during the development of chronic anthracycline-induced cardiomyopathy using an experimental rabbit modelMichaela Adamcova0Helena Parova1Olga Lencova-Popelova2Petra Kollarova-Brazdova3Ivana Baranova4Marcela Slavickova5Tereza Stverakova6Petra Sauer Mikyskova7Yvona Mazurova8Martin Sterba9Department of Physiology, Hradec Kralove, CzechiaDepartment of Clinical Biochemistry and Diagnostics, Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Hradec Kralove, CzechiaDepartment of Pharmacology, Hradec Kralove, CzechiaDepartment of Pharmacology, Hradec Kralove, CzechiaDepartment of Clinical Biochemistry and Diagnostics, Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Hradec Kralove, CzechiaDepartment of Clinical Biochemistry and Diagnostics, Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Hradec Kralove, CzechiaDepartment of Clinical Biochemistry and Diagnostics, Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Hradec Kralove, CzechiaDepartment of Clinical Biochemistry and Diagnostics, Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove, Hradec Kralove, CzechiaDepartment of Histology and Embryology, Charles University in Prague, Hradec Kralove, CzechiaDepartment of Pharmacology, Hradec Kralove, CzechiaBackground: 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.https://www.frontiersin.org/articles/10.3389/fphar.2023.1298172/fullanthracyclineschronic cardiomyopathycardiotoxicitymiRNAmyocardiumDNA damage response |
| spellingShingle | Michaela Adamcova Helena Parova Olga Lencova-Popelova Petra Kollarova-Brazdova Ivana Baranova Marcela Slavickova Tereza Stverakova Petra Sauer Mikyskova Yvona Mazurova Martin Sterba Cardiac miRNA expression during the development of chronic anthracycline-induced cardiomyopathy using an experimental rabbit model Frontiers in Pharmacology anthracyclines chronic cardiomyopathy cardiotoxicity miRNA myocardium DNA damage response |
| title | Cardiac miRNA expression during the development of chronic anthracycline-induced cardiomyopathy using an experimental rabbit model |
| title_full | Cardiac miRNA expression during the development of chronic anthracycline-induced cardiomyopathy using an experimental rabbit model |
| title_fullStr | Cardiac miRNA expression during the development of chronic anthracycline-induced cardiomyopathy using an experimental rabbit model |
| title_full_unstemmed | Cardiac miRNA expression during the development of chronic anthracycline-induced cardiomyopathy using an experimental rabbit model |
| title_short | Cardiac miRNA expression during the development of chronic anthracycline-induced cardiomyopathy using an experimental rabbit model |
| title_sort | cardiac mirna expression during the development of chronic anthracycline induced cardiomyopathy using an experimental rabbit model |
| topic | anthracyclines chronic cardiomyopathy cardiotoxicity miRNA myocardium DNA damage response |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1298172/full |
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