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Atrial overexpression of microRNA-27b attenuates angiotensin II-induced atrial fibrosis and fibrillation by targeting ALK5

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Abstract

Atrial fibrosis influences atrial fibrillation (AF) development by transforming growth factor beta 1 (TGF-β1)/Smad pathway. Although microRNAs are implicated in the pathogenesis of various diseases, information regarding the functional role of microRNAs in atrial dysfunction is limited. In the present study, we found that microRNA-27b (miR-27b) was the dominant member of miR-27 family expressed in left atrium. Moreover, the expression of miR-27b was significantly reduced after angiotensin II (AngII) infusion. Masson’s trichrome staining revealed that delivery of miR-27b adeno-associated virus to left atrium led to a decrease in atrial fibrosis induced by AngII. The increased expression of collagen I, collagen III, plasminogen activator inhibitor type 1 and alpha smooth muscle actin was also inhibited after miR-27b upregulation. In isolated perfused hearts, miR-27b restoration markedly attenuated AngII-induced increase in interatrial conduction time, AF incidence and AF duration. Furthermore, our data evidence that miR-27b is a novel miRNA that targets ALK5, a receptor of TGF-β1, through binding to the 3′ untranslated region of ALK5 mRNA. Ectopic miR-27b suppressed luciferase activity and expression of ALK5, whereas inhibition of miR-27b increased ALK5 luciferase activity and expression. Additionally, miR-27b inhibited AngII-induced Smad-2/3 phosphorylation without altering Smad-1 activity. Taken together, our study demonstrates that miR-27b ameliorates atrial fibrosis and AF through inactivation of Smad-2/3 pathway by targeting ALK5, suggesting miR-27b may play an anti-fibrotic role in left atrium and function as a novel therapeutic target for the treatment of cardiac dysfunction.

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Authors and Affiliations

  1. Department of Cardiology, Cangzhou Central Hospital, No. 201 Xinhua West Road, Yunhe District, Cangzhou, 061000, Hebei, China

    Yanshan Wang, Hongmei Li, Zhisheng Gao & Kunqing Song

  2. Department of Cardiology, Tianjin Medical University General Hospital, Tianjin, 300052, China

    Heng Cai

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  1. Yanshan Wang
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Correspondence to Yanshan Wang.

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All animal experiments were carried out according to the institutional guidelines from the Care and Use of Laboratory Animals of Cangzhou Central Hospital and were approved by the Institutional Animal Ethics Committee.

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Wang, Y., Cai, H., Li, H. et al. Atrial overexpression of microRNA-27b attenuates angiotensin II-induced atrial fibrosis and fibrillation by targeting ALK5. Human Cell 31, 251–260 (2018). https://doi.org/10.1007/s13577-018-0208-z

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  • DOI: https://doi.org/10.1007/s13577-018-0208-z

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