Reactive oxygen species mediated oxidative stress links diabetes and atrial fibrillation

Liang,Xue; Zhang,Qitong; Wang,Xinghua; Yuan,Meng; Zhang,Yue; Xu,Zhao; Li,Guangping; Liu,Tong

doi:10.3892/mmr.2018.8472

Reactive oxygen species mediated oxidative stress links diabetes and atrial fibrillation

Authors:
- Xue Liang
- Qitong Zhang
- Xinghua Wang
- Meng Yuan
- Yue Zhang
- Zhao Xu
- Guangping Li
- Tong Liu
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Affiliations: Tianjin Key Laboratory of Ionic‑Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China
Published online on: January 24, 2018 https://doi.org/10.3892/mmr.2018.8472
Pages: 4933-4940
Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diabetes is an independent risk factor for atrial fibrillation (AF); however, the underlying mechanism linking diabetes and AF remains to be clarified. The present study aimed to explore the molecular mechanism of increased reactive oxygen species (ROS) production in AF and the ROS‑mediated downstream events in diabetes. Firstly, the atrial fibroblasts were isolated from the left atrium of rabbits using enzyme digestion and differential adhesion. Then, the isolated cells were identified by morphology analysis under a microscope, collagen distribution using Masson trichrome staining and vimentin by immunofluorescence. Following this, the collected atrial fibroblasts were randomly divided into 7 groups and administered with high glucose (25 mM glucose), H2O2 stimulation (100 nmol/l), glucose + apocynin (100 µg/ml), H2O2 + apocynin, glucose + H2O2, and a combination of glucose, apocynin and H2O2, as well as the negative control (NC). An MTS assay was performed to investigate cell proliferation following the different treatments, and western blotting was conducted to explore the expression of several proteins including NAD(P)H oxidative (NOX) subunits, key factors involved in mitogen‑activated protein kinase (MAPK) signaling pathways and matrix metalloproteinases (MMPs). The atrial fibroblasts were spindle‑shaped with one or more protuberances. Vimentin was positively expressed in collected cells under confocal laser scanning microscopy. This result indicated that the atrial fibroblasts were successfully prepared. High glucose and H2O2 stimulation significantly increased the proliferation of atrial fibroblasts and apocynin markedly attenuated the promoting effects on cell proliferation induced by high glucose and H2O2 treatment (P<0.05). Additionally, high glucose and H2O2 stimulation increased the expression of Rac1, phospho(p)‑c‑Jun N‑terminal kinase 1, p38, p‑p38 and MMP9, which was markedly decreased by the addition of apocynin (P<0.05). The mechanism associated with diabetes and AF may be attributed to oxidative stress (ROS production) derived from NOX activity, and then induced activation of the MAPK signaling pathways and MMP9 expression.

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