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Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation
Published on: January 10, 2025
Down-Regulation of miR-327 Alleviates Ischemia/Reperfusion-Induced Myocardial Damage by Targeting RP105
Ying Yang1, Jun Yang2, Xiao-Wen Liu1
1Institute of Cardiovascular Diseases, China Three Gorges University, Yichang, China.
Background/Aims:
Micro RNAs (miRNAs) play a very important role in myocardial ischemia/ reperfusion injury (MIRI), including in inflammation, apoptosis, and angiogenesis. Previous studies have demonstrated up-regulation of miR-327 in renal ischemia/reperfusion injury and MIRI. Via TargetScan, we found RP105 is a possible target gene of miR-327; our previous studies have also confirmed that RP105 acted as a cardioprotective protein in MIRI by reducing inflammation. However, the regulatory effect of miR-327 on RP105 has not previously been proposed. In our study, we aimed to identify the regulatory effect of miR-327 on RP105 protein in MIRI rats.
Methods:
Sixty male Sprague-Dawley rats were randomly divided into five groups, which were pre-treated with saline (sham and ischemia/reperfusion group), adenovirus-expressing miR-327-RNAi (Ad-miR-327-i group), control (Ad-NC group), or pri-miR-327 (Ad-miR-327 group) treatments. Three days later, the rat MIRI model was established by ischemia for 30 min, followed by reperfusion for 3 h. Myocardium and plasma were harvested and assessed.
Results:
miR-327 was increased by nearly 3-fold both in myocardium and plasma, which down-regulated RP105 in a 3'-untranslated region-dependent manner, and down-regulation of miR-327 via adenovirus transfection indirectly suppressed the TLR4/ TLR2-MyD88-NF-κB signaling axis activation via up-regulation of RP105, which subsequently resulted in reduced myocardial infarct size, attenuated cardiomyocyte destruction, and alleviated inflammation. In contrast, up-regulation of miR-327 induced the opposite effect.
Conclusion:
Down-regulation of miR-327 exerts a cardioprotective effect against MIRI by reducing inflammation, which may constitute a promising molecular therapeutic target for treating MIRI.
Insights
Reducing miR-327 levels protects the heart from injury during myocardial ischemia/reperfusion. This involves up-regulating RP105, reducing inflammation, and improving outcomes in MIRI rats.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Inflammation Research
Background:
- MicroRNAs (miRNAs) are crucial in myocardial ischemia/reperfusion injury (MIRI), affecting inflammation, apoptosis, and angiogenesis.
- miR-327 is upregulated in MIRI, and RP105, a potential target, is cardioprotective.
- The regulatory relationship between miR-327 and RP105 in MIRI was previously uncharacterized.
Purpose of the Study:
- To investigate the regulatory effect of miR-327 on RP105 protein expression in a rat model of MIRI.
- To elucidate the underlying molecular mechanisms of miR-327's action in MIRI.
Main Methods:
- A rat model of MIRI was established.
- Rats were treated with saline, miR-327 inhibitors (Ad-miR-327-i), or miR-327 mimics (Ad-miR-327).
- Myocardial and plasma samples were analyzed for RP105 expression, inflammation markers, and infarct size.
Main Results:
- miR-327 levels increased significantly in MIRI myocardium and plasma.
- miR-327 directly down-regulated RP105 expression.
- Inhibition of miR-327 up-regulated RP105, suppressed the TLR4/TLR2-MyD88-NF-κB pathway, reduced infarct size, and alleviated myocardial damage and inflammation.
Conclusions:
- Down-regulation of miR-327 confers cardioprotection against MIRI.
- This protective effect is mediated by RP105 up-regulation and subsequent reduction in inflammation.
- miR-327 represents a potential molecular therapeutic target for MIRI.
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