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Angiotensin II Activates Signal Transducers and Activators of Transcription 3 via Rac1 in the Atrial Tissue in Permanent Atrial Fibrillation Patients with Rheumatic Heart Disease

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Abstract

Patients with rheumatic heart disease (RHD) often experience persistent atrial fibrillation (AF) associated with adverse atrial structural remodeling (ASR) manifested by atrial fibrosis and left atrial enlargement. The aim of this study was to explore the potential molecular signaling mechanisms for atrial fibrosis and ASR. Twenty RHD patients with persistent AF and 10 RHD patients with sinus rhythm (Group A) were recruited in our study, which all underwent transthoracic echocardiography. Right atrial appendage (RAA) tissue samples were obtained from these patients during mitral/aortic valve replacement operation. The AF patients were further divided into two groups according to left atrial diameter (LAD): Group B with LAD ranging 50–65 mm and Group C with LAD >65 mm. Histological examinations were performed with hematoxylin–eosin staining and Masson’s trichrome staining. Atrial angiotensin II (AngII) content was measured by ELISA. Rac1 and STAT3 protein levels were determined by Western blot analysis. Hematoxylin–eosin staining demonstrated highly organized arrangement of atrial muscles in control Group A and significant derangement in both Group B and C AF patients with reduced cell density and increased cell size. Moreover, Masson’s trichrome staining showed that atrial myocytes were surrounded by large trunks of collagen fibers in both Group B and C, but not in Group A. There was a positive correlation between atrial tissue fibrosis and LAD. AngII content was markedly higher in Group C than in Group B than in Group A, which was positively correlated with LAD. Similarly, Rac1 and STAT3 protein levels were found considerably higher in Group C and B than in Group A with excellent correlation to LAD. Our study unraveled for the first time the AngII/Rac1/STAT3 signaling as a mechanism for ASR thereby AF in a particular clinical setting―RHD patients with persistent AF and indicated inhibition of this pathway may help ameliorating adverse ASR.

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Authors and Affiliations

  1. Department of Cardiovascular Surgery, Shenyang Northern Hospital, 83 Wenhua Road, Shenhe District, Shenyang, 110016, Liaoning, China

    Xiao-Dong Xue & Hui-Shan Wang

  2. Department of Cardiothoracic Surgery, Ningxia People’s Hospital, 148 West Huaiyuan Road, Xixia District, Yinchuan, 750021, Ningxia, China

    Jian-Hua Huang

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Xue, XD., Huang, JH. & Wang, HS. Angiotensin II Activates Signal Transducers and Activators of Transcription 3 via Rac1 in the Atrial Tissue in Permanent Atrial Fibrillation Patients with Rheumatic Heart Disease. Cell Biochem Biophys 71, 205–213 (2015). https://doi.org/10.1007/s12013-014-0186-z

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