Abstract
Purpose: To investigate the effect of miR-486 on rats with acute myocardial infarction (AMI), and its mechanism of action.Methods: A rat model of AMI was established. They were randomly divided into 4 groups, namely, sham, model, agomiR-486 and antagomiR-486 groups, respectively. Rats in these different groups were treated with agomiR-21 (5 μL, 40 nmol/mL), antagomiR-21 (5 μL, 40 nmol/mL) or agomiR-NC (5 μL, 40 nmol/mL), respectively. Then, key miRNAs were sorted out using gene-chip assay and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. Luciferase reporter gene assay was conducted to determine the interaction between miR-486 and gene of PTEN. After intraperitoneal injection of agomiR-486 and antagomiR-486, hemodynamics was measured to determine the effect of miR-486 on myocardial function of the rats. The effect of miR-486 expression level on the expression of myocardial enzymes in serum, the morphology of myocardial tissues, and the apoptosis of myocardial tissues in rats, were investigated. Additionally, the effect of miR-486 expression level on PTEN/AKT signaling pathway in the rats was determined by Western blotting.Results: The results of gene-chip and qRT-PCR assays revealed that there were 8 differentially expressed genes in rat myocardial tissues in the model group when compared with the sham group. MiR-486 improved the cardiac function of rats and the morphology of myocardial tissues, but reduced AMI-induced apoptosis of myocardial cells and the expression of myocardial enzymes (markers of myocardial injury) in a dose-dependent manner (p < 0.05). The results of luciferase reporter gene assay showed that PTEN was a direct target of miR-486. In rat models of AMI, a raised expression of miR-486 remarkably suppressed the protein expression level of PTEN and up-regulated that of p-AKT/AKT (p < 0.05).Conclusion: MiR-486 protects against AMI in rats probably by targeting PTEN and activating the AKT signaling pathway. The results of the current study may provide new insights for the treatment of AMI.
Highlights
Coronary heart disease, known as ischemic heart disease, is one of the diseases with the highest morbidity and mortality rates worldwide, which manifests as the narrowing and remodeling of the coronary arteries, leading to ischemia and hypoxia in the myocardium and inducing acute myocardial infarction (AMI) [1]
QRT-PCR was used to determine the expression of differentially expressed Micro ribonucleic acids (miRNAs) in bone marrow tissues
The results showed that the fluorescence response intensity of HEK293 cells with wild-type PTEN transfected with miR-486 was remarkably weakened, while that of HEK293 cells with mutant PTEN had no evident changes
Summary
Known as ischemic heart disease, is one of the diseases with the highest morbidity and mortality rates worldwide, which manifests as the narrowing and remodeling of the coronary arteries, leading to ischemia and hypoxia in the myocardium and inducing acute myocardial infarction (AMI) [1]. Micro ribonucleic acids (miRNAs) are a class of non-coding RNAs with a small molecular weight, the mechanism of action of which is to bind to the 3'-untranslated region (3'-UTR) of messenger RNAs (mRNAs) to repress the expression of mRNAs or induce their degradation, modulating a series of important biological processes,x including energy metabolism and cell growth, survival and differentiation [4]. A total of 40 SD male rats weighing 180 - 200 g were housed in an SPF-grade animal room at 25 °C and a humidity of 45 % under a light-dark cycle of 12 h/ 12 h with free access to feed and water They were randomly divided into 4 groups, namely, sham, model, agomiR-486 and antagomiR-486 groups. The prepared paraffin sections were subjected to TUNEL staining in strict accordance with the instructions of the manufacturer's kit to determine the apoptosis level of myocardial tissues in each group of rats. Student's t-test was used for statistical analysis, and p < 0.05 was considered statistically significant
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