MiR-24 Alleviates MI/RI by Blocking the S100A8/TLR4/MyD88/NF-kB 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 because of the multifactorial disorders involved in MI/RI. MicroRNAs (miR-24) can achieve multitarget regulation in several diseases, suggesting that this factor may have ideal effects on alleviation of MI/RI. In the present study, bioinformatics method was used to screen potential therapeutic targets of miR-24 associated with MI/RI. Three days before ischemia/reperfusion surgery, rats in the ischemia/reperfusion, miR-24, and adenovirus-negative control groups were injected with saline, miR-24, and adenovirus-negative control (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 minutes of ischemia followed by reperfusion for 2 hours. 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 and lactate dehydrogenase release. Interestingly, miR-24 upregulation reduced S100A8 expression, followed by inhibition of toll-like receptor 4/MyD-88/nuclear factor-k-gene binding signaling activation. In conclusion, miR-24 can alleviate MI/RI via inactivation of the S100A8/toll-like receptor 4/MyD-88/nuclear factor-k-gene binding signaling pathway.