Hyperglycemia and Advanced Glycation End Products Regulate miR-126 Expression in Endothelial Progenitor Cells

    loading  Checking for direct PDF access through Ovid

Abstract

Background/Aims:

Dysfunction of endothelial progenitor cell (EPCs) contributes to diabetic vascular disease. We reported that downregulated miR-126 in diabetic patients causes EPC dysfunction. The study was designed to investigate how high glucose (HG) and advanced glycation end products (AGEs) regulate miR-126 expression and whether miR-126 mediates the effects of HG and AGEs on EPCs.

Methods:

We first tested the effects of glucose (5.5–50 mM) and AGEs at 50–200 mg/l on EPC proliferation and selected HG at 50 mM and AGEs at 50 mg/l for further experiments. EPCs were stimulated with HG and AGEs, and miR-126 expression was measured by real-time PCR. Reactive oxygen species (ROS) were measured by immunofluorescence microscopy and flow cytometry. IL-6 and TNF-α levels in EPC supernatants were determined by ELISA. The effects of miR-126 on ROS and inflammatory markers under stimulation of HG and AGEs were also assessed. Finally, the effects of inhibitors of PI3K and Akt on AGE-mediated miR-126 expression were examined.

Results:

HG and AGEs increased IL-6, TNF-α and ROS and decreased miR-126 expression in EPCs. miR-126 negatively regulated IL-6, TNF-α and ROS. miR-126 overexpression reduced and miR-126 inhibition further increased the inflammatory markers and ROS induced by HG and AGEs. Inhibitors of PI3K and Akt further decreased miR-126 expression in the presence of AGEs.

Conclusions:

In conclusion, hyperglycemia and AGEs decrease miR-126 expression in EPCs. Recovering miR-126 expression may protect EPCs against dysfunction induced by HG and AGEs.

Related Topics

    loading  Loading Related Articles