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MicroRNA-1 downregulation by propranolol in a rat model of myocardial infarction: a new mechanism for ischaemic cardioprotection.
MedLine Citation:
PMID:  19581315     Owner:  NLM     Status:  In-Process    
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.
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-06
Journal Detail:
Title:  Cardiovascular research     Volume:  84     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  434-41     Citation Subset:  IM    
Department of Pharmacology , Harbin Medical University, Harbin, Heilongjiang 150081, People's Republic of China.
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