Galectin-3 Induces Atrial Fibrosis by Activating the TGF-β1/Smad Pathway in Patients with Atrial Fibrillation

被引：37
作者：
Xiao, Minghan [1 ]
Zhang, Meixia [1 ]
Bie, Mengjun [1 ]
Wang, Xiaowen [1 ]
Guo, Jingwen [1 ]
Xiao, Hua [1 ]
机构：
[1] Chongqing Med Univ, Dept Cardiol, Affiliated Hosp 1, 1 Med Coll Rd, Chongqing 400016, Peoples R China
来源：
CARDIOLOGY | 2020年 / 145卷 / 07期
基金：
中国国家自然科学基金;
关键词：
Atrial fibrosis; Atrial fibrillation; Galectin-3; TGF-beta; 1; CATHETER ABLATION; HEART-FAILURE; MECHANISMS; EXPRESSION; OVEREXPRESSION; FIBROBLASTS; MYOCARDIUM; DISEASE;
D O I：
10.1159/000506072
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Background:Atrial fibrosis plays a critical role in the occurrence and maintenance of atrial fibrillation. The role of TGF-beta 1 in mediating atrial fibrosis is well documented. The beta-galactoside-binding lectin galectin-3 (Gal-3) is mainly produced by macrophages in biological events such as inflammation and angiogenesis. Previous studies have shown that Gal-3 is associated with atrial fibrosis, but the relationship between TGF-beta 1 and Gal-3 in atrial fibrosis remains unclear.Objective:To determine whether Gal-3 induces atrial fibrosis and atrial fibrillation by activating the TGF-beta 1/Smad pathway and whether the expression of Gal-3 is mediated by TGF-beta 1, which can enable assessing the relationship between Gal-3 and TGF-beta 1 in atrial fibrosis.Methods:In this study, 30 patients' right atrial appendages were collected and divided into 3 groups: congenital heart disease sinus rhythm group (n= 10, as a control group), rheumatic heart disease sinus rhythm group (n= 10), and rheumatic heart disease atrial fibrillation group (n= 10). Rat atrial fibroblasts were cultured in vitro, and recombinant Gal-3 and recombinant TGF-beta 1 proteins were added to the cell culture. The expression of Gal-3, TGF-beta 1, Smad2, and collagen I was detected by Western blotting and quantitative real-time PCR. Atrial tissues were stained with Masson's trichrome stain to evaluate the extent of atrial fibrosis. The expression of Gal-3 and TGF-beta 1 was detected by immunohistochemical staining and immunofluorescence staining. Gal-3 and TGF-beta 1 interaction was demonstrated by immunoprecipitation.Results:The expression levels of Gal-3, TGF-beta 1, Smad2, and collagen I were elevated in the rheumatic heart disease atrial fibrillation group compared with the congenital heart disease sinus rhythm group and the rheumatic heart disease sinus rhythm group. In cultured atrial fibroblasts, there is a synergistic interaction between Gal-3 and TGF-beta 1. Gal-3 stimulated the TGF-beta 1/Smad pathway, and overexpression of TGF-beta 1 induced Gal-3 expression.Conclusions:Gal-3 and TGF-beta 1 interact with each other and stimulate the downstream TGF-beta 1/Smad pathway. This finding suggests that Gal-3 could be an important factor in TGF-beta 1-induced fibrosis in atrial fibrillation. (c) 2020 S. Karger AG, Basel
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收藏
页码：446 / 455
页数：10
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