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

Abstract

<b>Objective:</b> Present study focused on the influence of lncRNA <i>MALAT1</i> on coronary atherosclerotic heart disease (CAD) by regulating miR-15b-5p/<i>MAPK1</i> and mTOR signaling pathway.<b>Method:</b> Differentially expressed genes and activated pathway were investigated through bioinformatics analysis. QRT-PCR was conducted to verify expression of <i>MALAT1</i>, miR-15b-5p and <i>MAPK1</i> in CAD blood samples and endothelial progenitor cells (EPCs). In addition, the interactions among <i>MALAT1</i>, miR-15b-5p and <i>MAPK1</i> 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 <i>MALAT1</i> on cell autophagy and atherogenesis was tested <i>in vivo</i>.<b>Results:</b><i>MALAT1</i> was overexpressed in CAD blood samples and EPCs. Knockdown of <i>MALAT1</i> and <i>MAPK1</i> promoted cell viability, autophagy and further suppressed the development of CAD. Antago<i>MALAT1</i> protects mice against atherosclerosis.<b>Conclusion:</b> LncRNA <i>MALAT1</i> inhibited EPCs autophagy and increased cell viability while repressed apoptosis of CAD via activating mTOR signaling pathway.