Xiao-Qing Chen1, Dao-Liang Zhang1, Ming-Jian Zhang2, Meng Guo2, Yang-Yang Zhan2, Fang Liu2, Wei-Feng Jiang1, Li Zhou1, Liang Zhao3, Quan-Xing Wang4, Xu Liu5. 1. Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, PR China. 2. National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, PR China. 3. Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, PR China. Electronic address: zhaol_zg@163.com. 4. National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, PR China. Electronic address: wqxejd@126.com. 5. Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, PR China. Electronic address: liuxu_xk@163.com.
Abstract
AIMS: Atrial fibroblasts and macrophages have long been thought to participate in atrial fibrillation (AF). However, which specific mediator may regulate the interaction between them remains unclear. METHODS AND RESULTS: We provided the evidence for the involvement of Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF), an important inflammation-related molecule, in the pathophysiology of AF. Patients with AF showed higher levels of angiotensin II (AngII) and TRIF expression and larger number of macrophages infiltration in left atria appendage than individuals with sinus rhythm (SR). In the cell study, AngII induced chemokines expressions in mouse atrial fibroblasts and AngII-stimulated atrial fibroblasts induced the chemotaxis of macrophages, which were reduced by losartan and TRIF siRNA. Meanwhile, AngII-stimulated atrial fibroblasts proliferation was enhanced by macrophages. CONCLUSIONS: Our data demonstrated that TRIF may be a crucial factor promoting the interaction between atrial fibroblasts and macrophages, leading to atrial fibrosis.
AIMS: Atrial fibroblasts and macrophages have long been thought to participate in atrial fibrillation (AF). However, which specific mediator may regulate the interaction between them remains unclear. METHODS AND RESULTS: We provided the evidence for the involvement of Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF), an important inflammation-related molecule, in the pathophysiology of AF. Patients with AF showed higher levels of angiotensin II (AngII) and TRIF expression and larger number of macrophages infiltration in left atria appendage than individuals with sinus rhythm (SR). In the cell study, AngII induced chemokines expressions in mouse atrial fibroblasts and AngII-stimulated atrial fibroblasts induced the chemotaxis of macrophages, which were reduced by losartan and TRIF siRNA. Meanwhile, AngII-stimulated atrial fibroblasts proliferation was enhanced by macrophages. CONCLUSIONS: Our data demonstrated that TRIF may be a crucial factor promoting the interaction between atrial fibroblasts and macrophages, leading to atrial fibrosis.