Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

MiR-486 protects against acute myocardial infarction via regulation of PTEN

Qinfeng Han¹, Zhong Xu¹, Xiaolei Zhang¹, Kun Yang, Zhifei Sun¹, Weidong Sun¹, Wanbo Liu²

¹The Third Department of Cardiovascular Medicine, Taian City Central Hospital, Taian; ²Department of Internal Medicine, Zhantansi Outpatient, Central Medical Brunch of PLA General Hospital, Beijing, China.

For correspondence:- Wanbo Liu Email: liuwanbo200@163.com Tel:+86018010216753

Accepted: 23 August 2021 Published: 30 September 2021

Citation: Han Q, Xu Z, Zhang X, Yang K, Sun Z, Sun W, et al. MiR-486 protects against acute myocardial infarction via regulation of PTEN. Trop J Pharm Res 2021; 20(9):1845-1853 doi: 10.4314/tjpr.v20i9.10

© 2021 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

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.

Keywords: miR-486, PTEN, Acute myocardial infarction, p-AKT/AKT, Gene chip, PTEN/AKT signaling pathway