MicroRNA‑221‑3p contributes to cardiomyocyte injury in H2O2‑treated H9c2 cells and a rat model of myocardial ischemia‑reperfusion by targeting p57.

Myocardial ischemia‑reperfusion (I/R) injury is a major cause of cardiovascular disease worldwide, and microRNAs have been implicated in the regulation of pathological and physiological processes in myocardial I/R injury. The present study aimed to investigate the role of microRNA (miR)‑221‑3p in myocardial I/R injury. Cell death and lactate dehydrogenase (LDH) activity were increased in hydrogen peroxide (H2O2)‑treated H9c2 cells, as measured by flow cytometry and an LDH detection kit. The expression of miR‑221‑3p was elevated in H2O2‑incubated cells and in remote areas of the rat I/R model, examined using reverse transcription‑quantitative polymerase chain reaction analysis. The overexpression of miR‑221‑3p enhanced the number of propidium iodide (PI)+ cells and the activity of LDH in H2O2‑treated cells. In I/R‑induced rats, the overexpression of miR‑221‑3p promoted the number of myosin+ cells and inhibited the fractional shortening of left ventricular diameter (FSLVD%). The results showed that the expression of p57 at the gene and protein levels was decreased in H9c2 cells incubated with H2O2 and in rats subjected to I/R surgery; the expression of p57 decreased following the overexpression of miR‑221‑3p. Subsequently, the hypothesis that p57 was the direct target of miR‑221‑3p was confirmed by performing a dual‑luciferase reporter assay. Finally, to examine the function of p57 in myocardial impairment, p57 was transfected into H9c2 cells and administered to the rats prior to undergoing H2O2 treatment and I/R surgery, respectively. The results indicated that p57 attenuated the number of PI+ cells and the activity of LDH in H2O2‑treated cells, whereas p57 downregulated the number of myosin+ cells and upregulated FSLVD% in the I/R‑treated rats. Therefore, these findings suggested that miR‑221‑3p exacerbated the H2O2‑induced myocardial damage in H9c2 cells and myocardial I/R injury in the rat model by modulating p57.

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