miR‑101a‑3p overexpression prevents acetylcholine‑CaCl<sub>2</sub>‑induced atrial fibrillation in rats via reduction of atrial tissue fibrosis, involving inhibition of EZH2

Zhu,Jing; Zhu,Ning; Xu,Jian

doi:10.3892/mmr.2021.12380

miR‑101a‑3p overexpression prevents acetylcholine‑CaCl₂‑induced atrial fibrillation in rats via reduction of atrial tissue fibrosis, involving inhibition of EZH2

Authors:
- Jing Zhu
- Ning Zhu
- Jian Xu
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Affiliations: Department of Cardiology, The First Affiliated Hospital of USTC, Hefei, Anhui 230001, P.R. China, Department of Respiratory Medicine, Ningbo First Hospital, Ningbo, Zhejiang 315010, P.R. China
Published online on: August 20, 2021 https://doi.org/10.3892/mmr.2021.12380
Article Number: 740
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Atrial fibrillation (AF), a clinically common heart arrhythmia, can result in left ventricular hypofunction, embolism and infarction. MicroRNA (miR)‑101a‑3p is lowly expressed in atrial tissues of patients with AF, but its role in AF remains unknown. In the present study, an AF model in rats was established via intravenous injection of acetylcholine (Ach)‑CaCl₂. The downregulation of miR‑101a‑3p and upregulation of enhancer of zeste 2 homolog 2 (EZH2) were observed in AF model rats, indicating the involvement of miR‑101a‑3p and EZH2 in AF development. To study the effect of miR‑101a‑3p on AF in vivo, AF model rats were intramyocardially injected with lentivirus expressing miR‑101a‑3p. Electrocardiogram analysis identified that miR‑101a‑3p overexpression restored disappeared P wave and R‑R interphase changes in Ach‑CaCl₂‑induced rats. Overexpression of miR‑101a‑3p also increased the atrial effective refractory period, reduced AF incidence and shortened duration of AF. Histological changes in atrial tissues were observed after H&E and Masson staining, which demonstrated that miR‑101a‑3p reduced atrial remodeling and fibrosis in AF model rats. Moreover, EZH2 expression was downregulated in atrial tissues by miR‑101a‑3p induction. Immunohistochemistry for collagen Ⅰ and collagen III revealed a reduction in atrial collagen synthesis following miR‑101a‑3p overexpression in AF model rats. Additionally, miR‑101a‑3p lowered the expression of pro‑fibrotic biomarkers, including TGF‑β1, connective tissue growth factor, fibronectin and α‑smooth muscle actin. The luciferase reporter assay results also indicated that EZH2 was a target gene of miR‑101a‑3p. Taken together, it was found that miR‑101a‑3p prevented AF in rats possibly via inhibition of collagen synthesis and atrial fibrosis by targeting EZH2, which provided a potential target for preventing AF.

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