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Cardiovasc Res. 2009 Dec 1;84(3):434-41. doi: 10.1093/cvr/cvp232. Epub 2009 Jul 6.

MicroRNA-1 downregulation by propranolol in a rat model of myocardial infarction: a new mechanism for ischaemic cardioprotection.

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1
Department of Pharmacology , Harbin Medical University, Harbin, Heilongjiang 150081, People's Republic of China.

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 AND RESULTS:

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.

PMID:
19581315
DOI:
10.1093/cvr/cvp232
[Indexed for MEDLINE]
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