miRNA-541-5p regulates myocardial ischemia-reperfusion injury by targeting ferroptosis

Abstract Background Ferroptosis is recognized as a significant mechanism underlying myocardial ischemia‒reperfusion (I/R) injury. An increasing number of studies suggest that targeting iron death could be a new therapeutic approach. Currently, because of the mechanism of iron death, the mechanism of I/R injury via microRNA-targeted treatment has not been fully confirmed. Methods To establish a myocardial I/R model in SD rats. Deferoxamine was administered (100 mg/kg). The successful establishment of the rat I/R model was determined by histopathological analysis. Oxidative stress indices and iron death factors in rat serum or myocardial tissue were detected by ELISA, immunofluorescence and RT‒PCR. Differential target genes were subsequently screened via the sequencing of myocardial tissue miRNAs. In addition, rat H9C2 cardiomyocytes were cultured, and a target gene adenovirus vector was constructed. Changes in the cell survival rate, oxidative stress indices and iron death factors were detected by CCK8, Western blot, ELISA, immunofluorescence and RT‒PCR, respectively. Results In this study, to confirm the occurrence of iron death in the myocardial tissue of a rat model of myocardial I/R injury, the target gene miRNA-541-5p was screened via miRNA sequencing, and the level of miRNA-541-5p was greater in the myocardium of the I/R injury model group than in those of the control and DFO groups. Finally, further verification through cell experiments revealed that the overexpression of miRNA-541-5p can significantly inhibit the viability of cardiomyocytes and promote the accumulation of the oxidation product ROS, causing iron overload in cardiomyocytes and exacerbating cardiomyocyte damage, whereas reducing miRNA-541-5p expression can reverse this pathological condition. Conclusion In summary, miRNA-541-5p may be a biomarker of myocardial I/R damage diseases and can regulate oxidative stress and iron death by inhibiting the expression of miRNA-541-5p, thereby reducing the mechanisms of I/R injury.