MiR-291b-3p mediated ROS-induced endothelial cell dysfunction by targeting HUR

Abstract

Endothelial dysfunction is an early marker of atherosclerosis. Previous studies have indicated that microRNA (miR)-291b-3p regulates the metabolism of lipids and glucose in the liver via targeting adenosine monophosphate-activated kinase α1 and transcription factor p65. The present study investigated whether miR-291b-3p mediated H2O2-mediated endothelial dysfunction. The level of apoptosis of EOMA mouse endothelial cells was analyzed by terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling staining. The mRNA levels of miR-291b-3p, intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) were determined by quantitative polymerase chain reaction. The level of phosphorylated extracellular signal-regulated kinase, and levels of B-cell lymphoma 2 (Bcl-2)-associated X protein and Bcl-2 protein were detected by western blot analysis. The treatment of H2O2 induced the apoptosis and increased the mRNA levels of miR-291b-3p, ICAM-1 and VCAM-1 in EOMA cells. It was also demonstrated that the overexpression of miR-291b-3p promoted EOMA cell apoptosis and dysfunction. In contrast, the downregulation of miR-291b-3p rescued the effect of H2O2 on EOMA cell dysfunction. In addition, Hu antigen R (HuR) was identified as a target gene of miR-291b-3p in EOMA cells. The overexpression of HuR reversed the endothelial dysfunction induced by miR-291b-3p mimics. The present study provides novel insight into the critical role of miR-291b-3p on the endothelial dysfunction induced by H2O2. miR-291b-3p may mediate H2O2-induced endothelial dysfunction via targeting HuR.