miR-24 alleviates MI/RI by blocking the S100A8/TLR4/MyD88/NF-κB pathway.

ABSTRACT Although inflammation plays an important role in myocardial ischemia/reperfusion injury (MI/RI), an anti-inflammatory treatment with a single target has little clinical efficacy due to the multifactorial disorders involved in MI/RI. miR-24 can achieve multitarget regulation in several diseases, suggesting that this factor may have ideal effects on alleviation of MI/RI. In present study, bioinformatics method was used to screen potential therapeutic targets of miR-24 associated with MI/RI. Three days before ischemia/reperfusion (I/R) surgery, rats in the I/R, miR-24 and adenovirus-negative control (Ad-NC) groups were injected with saline, miR-24, and Ad-NC (0.1 mL of 5 × 109 PFU/mL), respectively. Myocardial enzymes, myocardial infarct size, cardiac function, and the possible molecular mechanism were subsequently analyzed. In contrast to the level of S100A8, the level of miR-24 in myocardial tissue was significantly reduced after 30 min of ischemia followed by reperfusion for 2 h. Overexpression of miR-24 reduced the myocardial infarction area and improved the heart function of rats 3 days after MI/RI. Moreover, miR-24 inhibited infiltration of inflammatory cells in the peri-infarction area and decreased creatine kinase myocardial band (CK-MB) and lactate dehydrogenase (LDH) release. Interestingly, miR-24 upregulation reduced S100A8 expression, followed by inhibition of TLR4/MyD-88/NF-κB signaling activation. In conclusion, miR-24 can alleviate MI/RI via inactivation of the S100A8/TLR4/MyD-88/NF-κB signaling pathway.