MicroRNA-126 and VEGF enhance the function of endothelial progenitor cells in acute myocardial infarction.

Abstract

Previous studies have found that microRNA-126 (miR-126) overexpression can exert beneficial effects on endothelial function and angiogenesis. The role of miR-126 was previously reported to be by directly limiting the activities of negative regulators of the vascular endothelial growth factor (VEGF) pathway, such as PI3K regulation subunit 2 (PIK3R2). The aim of the present study was to investigate the role of the miR-126/PIK3R2/VEGF axis in endothelial progenitor cells (EPCs) under hypoxic conditions. An in vitro hypoxia model in EPCs was established by exposing EPCs to hypoxia (O2/N2/CO2, 1/94/5) for 72 h, before reverse transcription-quantitative PCR (RT-qPCR) and western blot analyzes were used to measure miR-126 and PIK3R2 expression in EPCs. The proliferation, migration and tube-forming ability of the transfected cells were measured using MTT, Transwell and tube formation assays, respectively. miR-126 expression was found to be lower in EPCs in the hypoxia group compared with that in the control group (P<0.01). The expression of PIK3R2, a direct target gene of miR-126, was found to be higher in the hypoxia group compared with that in the control group (P<0.01). miR-126 mimic and VEGF-plasmid co-transfection improved the proliferation, migration, tube-forming ability and restored the phosphorylation of AKT in EPCs under hypoxic conditions (all P<0.01). In addition, the effects of miR-126 mimic on hypoxia-induced EPCs were reversed by PIK3R2-plasmid co-transfection, whilst the effects of VEGF-plasmid were enhanced further by co-transfection with the miR-126 mimic. In conclusion, miR-126 promoted the functions of EPCs under hypoxic conditions by negatively targeting PIK3R2, whilst the combined overexpression of miR-126 and VEGF enhanced these aforementioned effects.