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Research Paper

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

Li Y.a · Zhou Q.a · Pei C.a · Liu B.a · Li M.b · Fang L.c · Sun Y.a · Li Y.a · Meng S.a

Author affiliations

aDepartment of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, and bDepartment of Interventional Radiology, Tenth People's Hospital of Tongji University, Shanghai, China; cHaematopoiesis and Leukocyte Biology Laboratory, Baker Heart and Diabetes Research Institute, Melbourne, Vic., Australia

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J Vasc Res 2016;53:94-104

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Article / Publication Details

First-Page Preview
Abstract of Research Paper

Received: January 05, 2016
Accepted: July 26, 2016
Published online: September 28, 2016
Issue release date: October 2016

Number of Print Pages: 11
Number of Figures: 8
Number of Tables: 0

ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)

For additional information: https://www.karger.com/JVR

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.

© 2016 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Research Paper

Received: January 05, 2016
Accepted: July 26, 2016
Published online: September 28, 2016
Issue release date: October 2016

Number of Print Pages: 11
Number of Figures: 8
Number of Tables: 0

ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)

For additional information: https://www.karger.com/JVR


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