Cardioprotective effects of miR-34a silencing in a rat model of doxorubicin toxicity.
Sci Rep
; 10(1): 12250, 2020 07 23.
Article
em En
| MEDLINE
| ID: mdl-32704131
ABSTRACT
Cardiotoxicity remains a serious problem in anthracycline-treated oncologic patients. Therapeutic modulation of microRNA expression is emerging as a cardioprotective approach in several cardiovascular pathologies. MiR-34a increased in animals and patients exposed to anthracyclines and is involved in cardiac repair. In our previous study, we demonstrated beneficial effects of miR-34a silencing in rat cardiac cells exposed to doxorubicin (DOXO). The aim of the present work is to evaluate the potential cardioprotective properties of a specific antimiR-34a (Ant34a) in an experimental model of DOXO-induced cardiotoxicity. Results indicate that in our model systemic administration of Ant34a completely silences miR-34a myocardial expression and importantly attenuates DOXO-induced cardiac dysfunction. Ant34a systemic delivery in DOXO-treated rats triggers an upregulation of prosurvival miR-34a targets Bcl-2 and SIRT1 that mediate a reduction of DOXO-induced cardiac damage represented by myocardial apoptosis, senescence, fibrosis and inflammation. These findings suggest that miR-34a therapeutic inhibition may have clinical relevance to attenuate DOXO-induced toxicity in the heart of oncologic patients.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doxorrubicina
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Predisposição Genética para Doença
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Inativação Gênica
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MicroRNAs
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Cardiotoxicidade
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Antibióticos Antineoplásicos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article