Highlights
- •MiR-24 up-regulation inhibits HG-stimulated oxidative stress of VSMCs.
- •MiR-24 up-regulation promotes reendothelialization in balloon-injured diabetic rats.
- •MiR-24 up-regulation inhibits Ogt and keap1 expression, and promotes Nrf2 and Ho-1 expression.
Abstract
Background and aims
The process of endothelial repair in diabetic patients after stent implantation was
significantly delayed compared with that in non-diabetic patients, and oxidative stress
is increasingly considered to be relevant to the pathogenesis of diabetic endothelial
repair. However, the mechanisms linking diabetes and reendothelialization after vascular
injury have not been fully elucidated. The aim of this study was to evaluate the effect
of microRNA-24 (miR-24) up-regulation in delayed endothelial repair caused by oxidative stress after balloon
injury in diabetic rats.
Methods
In vitro, vascular smooth muscle cells (VSMCs) isolated from the thoracic aorta were stimulated
with high glucose (HG) after miR-24 recombinant adenovirus (Ad-miR-24-GFP) transfection for 3 days. In vivo, diabetic rats induced using high-fat diet (HFD) and low-dose streptozotocin (30 mg/kg)
underwent carotid artery balloon injury followed by Ad-miR-24-GFP transfection for 20 min.
Results
The expression of miR-24 was decreased in HG-stimulated VSMCs and balloon-injured carotid arteries of diabetic
rats, which was accompanied by increased expression of Ogt and Keap1 and decreased expression of Nrf2 and Ho-1. Up-regulation of miR-24 suppressed VSMC oxidative stress induced by HG in vitro, and miR-24 up-regulation promoted reendothelialization in balloon-injured diabetic rats. The
underlying mechanism was related to the activation of the Nrf2/Ho-1 signaling pathway,
which subsequently suppressed intracellular reactive oxidative species (ROS) production
and malondialdehyde (MDA) and NADPH oxidase (Nox) activity, and to the restoration
of Sod and Gsh-px activation.
Conclusions
The up-regulation of miR-24 significantly promoted endothelial repair after balloon injury through inhibition
of oxidative stress by activating the Nrf2/Ho-1 signaling pathway.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: September 09, 2019
Accepted:
August 30,
2019
Received in revised form:
August 30,
2019
Received:
March 9,
2019
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
