MALAT1/miR-15b-5p/MAPK1 mediates endothelial progenitor cells autophagy and affects coronary atherosclerotic heart disease via mTOR signaling pathway.

Ying Zhu,Jinlan Duan,Tianrui Yang,Ninghui Mu,Tong Zhang

doi:10.18632/aging.101766

MALAT1/miR-15b-5p/MAPK1 mediates endothelial progenitor cells autophagy and affects coronary atherosclerotic heart disease via mTOR signaling pathway.

Ying Zhu, Jinlan Duan + Show 3 more

Open Access

https://doi.org/10.18632/aging.101766

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Abstract

Objective: Present study focused on the influence of lncRNA MALAT1 on coronary atherosclerotic heart disease (CAD) by regulating miR-15b-5p/MAPK1 and mTOR signaling pathway.Method: Differentially expressed genes and activated pathway were investigated through bioinformatics analysis. QRT-PCR was conducted to verify expression of MALAT1, miR-15b-5p and MAPK1 in CAD blood samples and endothelial progenitor cells (EPCs). In addition, the interactions among MALAT1, miR-15b-5p and MAPK1 were revealed by Luciferase reporter assay. Cell autophagy of EPCs was examined by Cyto-ID Autophagy Detection Kit and transmission electron microscope. MTT assay and flow cytometry were carried out to assess cell viability and apoptosis in different interference conditions. Western blot was performed to testify the expression of pERK1/2 (MAPK1), phosphorylated mTOR, ATG1 and LC3-II. Vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were detected by qRT-PCR. Finally, the effect of lncRNA MALAT1 on cell autophagy and atherogenesis was tested in vivo.Results: MALAT1 was overexpressed in CAD blood samples and EPCs. Knockdown of MALAT1 and MAPK1 promoted cell viability, autophagy and further suppressed the development of CAD. AntagoMALAT1 protects mice against atherosclerosis.Conclusion: LncRNA MALAT1 inhibited EPCs autophagy and increased cell viability while repressed apoptosis of CAD via activating mTOR signaling pathway.

Highlights

Coronary heart disease is primarily induced by atherosclerosis which is a systemic degenerative inflammatory vascular disease [1]
The GSE18608 data analysis illustrated that Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was up-regulated, which was one of the differentially expressed Long non-coding RNA (lncRNA) in coronary atherosclerotic heart disease (CAD) blood samples and endothelial progenitor cells (EPCs)
Results showed that miR-15b-5p serves as a target of MALAT1 and that miR-15b-5p can directly target to mitogen-activated protein kinase 1 (MAPK1)

Summary

Introduction

Coronary heart disease is primarily induced by atherosclerosis which is a systemic degenerative inflammatory vascular disease [1]. Coronary atherosclerotic heart disease (CAD) has a quite long history on its development, with a subclinical period. About half of all patients who die from coronary heart disease have no prior diagnosis or symptoms of cardiac disease [2]. During the several decades from 1900 to 1960, number of coro nary heart disease deaths had a great increase, which obtained a close attention by many researchers. Some of them thought that the increase of incidence in coronary atherosclerosis is the key reason for the marked increase in deaths [3]. Researches showed cell autophagy impairs atherosclerosis process while defective autophagy in cells enhances atherosclerosis [5, 6]

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Conclusion