Jing Zhang1, Wanyin Cai1, Zhixing Fan2, Chaojun Yang1, Wei Wang1, Mengting Xiong1, Cong Ma1, Jian Yang3. 1. Central Laboratory, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China; Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China; Yichang Key Laboratory of Ischemic Cardiovascular and Cerebrovascular Disease Translational Medicine, China. 2. Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China; Yichang Key Laboratory of Ischemic Cardiovascular and Cerebrovascular Disease Translational Medicine, China. 3. Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China; Yichang Key Laboratory of Ischemic Cardiovascular and Cerebrovascular Disease Translational Medicine, China. Electronic address: yangjian@ctgu.edu.cn.
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.
BACKGROUND AND AIMS: The process of endothelial repair in diabeticpatients after stent implantation was significantly delayed compared with that in non-diabeticpatients, 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 diabeticrats. 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, diabeticrats 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 diabeticrats, 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 diabeticrats. 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.
Authors: Adam Włodarski; Justyna Strycharz; Adam Wróblewski; Jacek Kasznicki; Józef Drzewoski; Agnieszka Śliwińska Journal: Int J Mol Sci Date: 2020-09-20 Impact factor: 5.923