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Updated: May 16, 2026
In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
Published on: June 15, 2018
Increased expression of microRNA-146a decreases myocardial ischaemia/reperfusion injury
Xiaohui Wang1, Tuanzhu Ha, Li Liu
1Department of Surgery, James H. Quillen College of Medicine, East Tennessee State University, Campus Box 70575, Johnson City, TN 37614-0575, USA.
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.
Insights
MicroRNA-146a protects the heart from ischemia/reperfusion injury by reducing infarct size and improving cardiac function. This protection is achieved by suppressing key inflammatory pathways and targets like IRAK1 and TRAF6.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- MicroRNA Therapeutics
Background:
- Myocardial ischemia/reperfusion (I/R) injury is a significant clinical challenge.
- Toll-like receptor pathways, including TLR4 and TLR2, play a role in I/R injury.
- Nuclear factor KappaB (NF-κB) activation is a key mediator of I/R-induced damage.
Purpose of the Study:
- To investigate the protective role of microRNA-146a (miR-146a) in myocardial I/R injury.
- To elucidate the underlying molecular mechanisms of miR-146a-mediated protection.
Main Methods:
- Lentivirus expressing miR-146a (LmiR-146a) was transfected into mouse hearts.
- Hearts were subjected to a controlled period of ischemia followed by reperfusion.
- Infarct size, cardiac function (ejection fraction, fractional shortening), apoptosis, and inflammatory markers were assessed.
Main Results:
- LmiR-146a transfection significantly reduced myocardial infarct size by 55%.
- miR-146a preserved cardiac function and attenuated I/R-induced apoptosis and caspase activity.
- Transfection suppressed IRAK1 and TRAF6 expression, inhibiting NF-κB activation and inflammatory cytokine production.
Conclusions:
- MicroRNA-146a confers significant protection to the myocardium against I/R injury.
- The protective effects are mediated through the suppression of IRAK1 and TRAF6, leading to reduced NF-κB activation and inflammation.
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