Skip Navigation



Cardiovascular Research Advance Access [Accepted Manuscript] published online on July 6, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp232
This Article
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
84/3/434    most recent
cvp232v2
cvp232v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Lu, Y.
Right arrow Articles by Yang, B.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lu, Y.
Right arrow Articles by Yang, B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

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

Yanjie Lu1,2, Yong Zhang1,2, Hongli Shan1,2, Zhenwei Pan1, Xuelian Li1, Baoxin Li1, Chaoqian Xu1, Bisi Zhang1, Fengmin Zhang1, Deli Dong1, Wuqi Song1, Guofen Qiao1 and Baofeng Yang1,2

1 Department of Pharmacology (State-Province Key Laboratories of Biomedicine and Pharmaceutics)
2 Institute of Cardiovascular Research, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China

Correspondence to: Baofeng Yang, Department of Pharmacology (State-Province Key Laboratories of Biomedicine and Pharmaceutics), Harbin Medical University, Heilongjiang 150081, P. R. China. Phone: 86-451-86671354; Fax: 86-451-86675769, E-mail: yangbf{at}ems.hrbmu.edu.cn

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 (MI) by coronary artery occlusion. Overexpression of miR-1 was observed in ischemic 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 ischemia, 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) signaling 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 ischemic myocardium. Moreover, propranolol inhibited the beta-adrenoceptor–cAMP–PKA signaling pathway and suppressed SRF expression.

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

Time for primary review: 38 Days

Yanjie Lu, Yong Zhang and Hongli Shan contributed equally to this work.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.