Xinyuan Han1, Shunda Wang2, Zhijun Yong2, Xueting Zhang2, Xuanqi Wang2. 1. Department of Rehabilitation Medicine, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Xi'an, 710068, Shaanxi Province, China. XinyuanHan0617@163.com. 2. Department of Rehabilitation Medicine, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Xi'an, 710068, Shaanxi Province, China.
Abstract
OBJECTIVE: Atrial fibrillation (AF) is a major cause of stroke with lifetime risks. microRNAs (miRNAs) are associated with AF attenuation, yet the mechanism remains unknown. This study investigated the functional mechanism of miR-29b in atrial fibrosis in AF. METHODS: The AF rat model was established by a 7-day intravenous injection of Ach-CaCl2 mixture. AF rats were injected with adeno-associated virus (AAv)-miR-29b and TGFβRΙ overexpression plasmid. AF duration was recorded by electrocardiogram. Atrial fibrosis was observed by Masson staining. Expressions of COL1A1, COL3A1, TGFβRΙ, TGFβΙ, miR-29b and Smad-2/3 pathway-related proteins in atrial tissues were detected by RT-qPCR and Western blot. Binding sites of miR-29b and TGFβRΙ were predicted and their target relationship was verified by dual-luciferase reporter assay. RESULTS: miR-29b was poorly expressed and expressions of COL1A1, COL3A1, TGFβRΙ, and TGFβ1 were increased in atrial tissues of AF rats. miR-29b overexpression alleviated atrial fibrosis, reduced expressions of COL1A1, COL3A1, and TGFβ1, and shortened AF duration in AF rats. TGFβRΙ was highly expressed in atrial tissues of AF rats. miR-29b targeted TGFβRΙ. TGFβRΙ overexpression overcame the improving effect of miR-29b overexpression on AF. miR-29b overexpression decreased ratios of p-Smad-2/3 and Smad-2/3 and inhibited the Smad-2/3 pathway. CONCLUSION: miR-29b might mitigate atrial fibrosis in AF rats by targeting TGFβRΙ and inhibiting the Smad-2/3 pathway.
OBJECTIVE: Atrial fibrillation (AF) is a major cause of stroke with lifetime risks. microRNAs (miRNAs) are associated with AF attenuation, yet the mechanism remains unknown. This study investigated the functional mechanism of miR-29b in atrial fibrosis in AF. METHODS: The AF rat model was established by a 7-day intravenous injection of Ach-CaCl2 mixture. AF rats were injected with adeno-associated virus (AAv)-miR-29b and TGFβRΙ overexpression plasmid. AF duration was recorded by electrocardiogram. Atrial fibrosis was observed by Masson staining. Expressions of COL1A1, COL3A1, TGFβRΙ, TGFβΙ, miR-29b and Smad-2/3 pathway-related proteins in atrial tissues were detected by RT-qPCR and Western blot. Binding sites of miR-29b and TGFβRΙ were predicted and their target relationship was verified by dual-luciferase reporter assay. RESULTS: miR-29b was poorly expressed and expressions of COL1A1, COL3A1, TGFβRΙ, and TGFβ1 were increased in atrial tissues of AF rats. miR-29b overexpression alleviated atrial fibrosis, reduced expressions of COL1A1, COL3A1, and TGFβ1, and shortened AF duration in AF rats. TGFβRΙ was highly expressed in atrial tissues of AF rats. miR-29b targeted TGFβRΙ. TGFβRΙ overexpression overcame the improving effect of miR-29b overexpression on AF. miR-29b overexpression decreased ratios of p-Smad-2/3 and Smad-2/3 and inhibited the Smad-2/3 pathway. CONCLUSION: miR-29b might mitigate atrial fibrosis in AF rats by targeting TGFβRΙ and inhibiting the Smad-2/3 pathway.
Authors: Felix Gramley; Johann Lorenzen; Eva Koellensperger; Klaus Kettering; Christian Weiss; Thomas Munzel Journal: Int J Cardiol Date: 2009-04-24 Impact factor: 4.164
Authors: Xiaoming Fan; Yingnyu Gao; Xiaolu Zhang; Haroon Y Lughmani; David J Kennedy; Steven T Haller; Sandrine V Pierre; Joseph I Shapiro; Jiang Tian Journal: PLoS One Date: 2020-12-17 Impact factor: 3.240