Document Detail


Increased expression of microRNA-146a decreases myocardial ischaemia/reperfusion injury.
MedLine Citation:
PMID:  23208587     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: We have reported that either toll-like receptor 4 deficiency (TLR4(-/-)) or TLR2 modulation protects against myocardial ischaemia/reperfusion (I/R) injury. The mechanisms involve attenuation of I/R-induced nuclear factor KappaB (NF-κB) activation. MicroRNA-146a (miR-146a) has been reported to target interleukin-1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6), resulting in inhibiting NF-κB activation. This study examined the role of microRNA-146a in myocardial I/R injury.
METHODS AND RESULTS: We constructed lentivirus expressing miR-146a (LmiR-146a). LmiR-146a was transfected into mouse hearts through the right common carotid artery. The 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 ischaemia (60 min) followed by reperfusion (4 h). Myocardial infarct size was analysed by triphenyltetrazolium chloride (TTC) staining. In separate experiments, the hearts were subjected to ischaemia (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: MicroRNA-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; Research Support, N.I.H., Extramural     Date:  2012-12-03
Journal Detail:
Title:  Cardiovascular research     Volume:  97     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-11     Completed Date:  2013-09-06     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  432-42     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Disease Models, Animal
Interleukin-1 Receptor-Associated Kinases / metabolism
Lentivirus / genetics
Mice
Mice, Knockout
MicroRNAs / genetics,  metabolism*
Myocardial Reperfusion Injury / metabolism*,  pathology,  prevention & control*
Myocardium / metabolism*,  pathology*
NF-kappa B / metabolism
TNF Receptor-Associated Factor 6 / metabolism
Toll-Like Receptor 4 / deficiency,  genetics,  metabolism
Transfection
Grant Support
ID/Acronym/Agency:
GM083016/GM/NIGMS NIH HHS; GM53522/GM/NIGMS NIH HHS; HL071837/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/MicroRNAs; 0/Mirn146 microRNA, mouse; 0/NF-kappa B; 0/TNF Receptor-Associated Factor 6; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 4; EC 2.7.11.1/Interleukin-1 Receptor-Associated Kinases; EC 2.7.11.1/Irak1 protein, mouse
Comments/Corrections

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