MicroRNA-1 downregulation by propranolol in a rat model of myocardial infarction: a new mechanism for ischaemic cardioprotection.
Cardiovasc Res
; 84(3): 434-41, 2009 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-19581315
ABSTRACT
AIMS:
The present study was designed to investigate whether the beneficial effects of beta-blocker propranolol are related to regulation of microRNA miR-1. METHODS ANDRESULTS:
We demonstrated that propranolol reduced the incidence of arrhythmias in a rat model of myocardial infarction by coronary artery occlusion. Overexpression of miR-1 was observed in ischaemic myocardium and strikingly, administration of propranolol reversed the up-regulation of miR-1 nearly back to the control level. In agreement with its miR-1-reducing effect, propranolol relieved myocardial injuries during ischaemia, restored the membrane depolarization and cardiac conduction slowing, by rescuing the expression of inward rectifying K(+) channel subunit Kir2.1 and gap junction channel connexin 43. Our results further revealed that the beta-adrenoceptor-cAMP-Protein Kinase A (PKA) signalling pathway contributed to the expression of miR-1, and serum response factor (SRF), which is known as one of the transcriptional enhancers of miR-1, was up-regulated in ischaemic myocardium. Moreover, propranolol inhibited the beta-adrenoceptor-cAMP-PKA signalling pathway and suppressed SRF expression.CONCLUSION:
We conclude that the beta-adrenergic pathway can stimulate expression of arrhythmogenic miR-1, contributing to ischaemic arrhythmogenesis, and beta-blockers produce their beneficial effects partially by down-regulating miR-1, which might be a novel strategy for ischaemic cardioprotection.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Propranolol
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Regulação para Baixo
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Receptores Adrenérgicos beta
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Isquemia Miocárdica
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Antagonistas Adrenérgicos beta
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MicroRNAs
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Infarto do Miocárdio
Tipo de estudo:
Incidence_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cardiovasc Res
Ano de publicação:
2009
Tipo de documento:
Article