期刊
CARDIOVASCULAR RESEARCH
卷 84, 期 3, 页码 434-441出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvp232
关键词
Propranolol; Arrhythmia; MicroRNA; Ion channels; Myocardial infarction
资金
- National Basic Research Program of China [2007CB512000 (2007CB512006), 2007CB516800 (2007CB516803)]
- National Nature Science Foundation of China [30672644]
The present study was designed to investigate whether the beneficial effects of beta-blocker propranolol are related to regulation of microRNA miR-1. 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. 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.
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