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Increased expression of microRNA-146a decreases myocardial ischemia/reperfusion injury.
MedLine Citation:
PMID:  23208587     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIMS: We have reported that either Toll-like receptor 4 deficiency (TLR4(-/-)) or TLR2 modulation protects against myocardial ischemia/reperfusion (I/R) injury. The mechanisms involve attenuation of I/R-induced nuclear factor KappaB (NF-κB) activation. MicroRNA-146a has been reported to target interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor associated factor 6 (TRAF6), resulting in inhibiting NF-κB activation. This study examined the role of microRNA-146a (miR-146a) in myocardial I/R injury.Methods and ResultsWe constructed lentivirus expressing miR-146a (LmiR-146a). LmiR-146a was transfected into mouse hearts through the right common carotid artery. Lentivirus vector (LmiR-Con) served as vector control. Untransfected mice served as I/R control. Sham operation served as sham control. Seven days after transfection, the hearts were subjected to ischemia (60 min) followed by reperfusion (4 hrs). Myocardial infarct size was analyzed by triphenyltetrazolium chloride (TTC) staining. In separate experiments, hearts were subjected to ischemia (60 min) followed by reperfusion for up to 7 days. Cardiac function was measured by echocardiography prior to I/R, 3 and 7 days after myocardial I/R. LmiR-146a transfection significantly decreased I/R-induced myocardial infarct size by 55% and prevented I/R-induced decreases in ejection fraction (EF%) and fractional shortening (%FS). LmiR-146a transfection attenuated I/R-induced myocardial apoptosis and caspase-3/7 and -8 activities. LmiR-146a transfection suppresses IRAK1 and TRAF6 expression in the myocardium. In addition, transfection of LmiR-146a prevented I/R-induced NF-κB activation and inflammatory cytokine production. CONCLUSIONS: miR-146a protects the myocardium from I/R injury. The mechanisms may involve attenuation of NF-κB activation and inflammatory cytokine production by suppressing IRAK1 and TRAF6.
Authors:
Xiaohui Wang; Tuanzhu Ha; Li Liu; Jianghuan Zou; Xia Zhang; John Kalbfleisch; Xiang Gao; David Williams; Chuanfu Li
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-3
Journal Detail:
Title:  Cardiovascular research     Volume:  -     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614.
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