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

Yanjie Lu, Yong Zhang, Hongli Shan, Zhenwei Pan, Xuelian Li, Baoxin Li, Chaoqian Xu, Bisi Zhang, Fengmin Zhang, Deli Dong, Wuqi Song, Guofen Qiao, Baofeng Yang
DOI: http://dx.doi.org/10.1093/cvr/cvp232 434-441 First published online: 6 July 2009


Aims The present study was designed to investigate whether the beneficial effects of β-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 β-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 β-adrenoceptor–cAMP–PKA signalling pathway and suppressed SRF expression.

Conclusion We conclude that the β-adrenergic pathway can stimulate expression of arrhythmogenic miR-1, contributing to ischaemic arrhythmogenesis, and β-blockers produce their beneficial effects partially by down-regulating miR-1, which might be a novel strategy for ischaemic cardioprotection.

  • Propranolol
  • Arrhythmia
  • MicroRNA
  • Ion channels
  • Myocardial infarction
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