OBJECTIVE: Atrial remodeling is involved in atrial fibrillation (AF), and atrial fibrosis is an important marker of atrial remodeling. On the basis of our previous animal studies of the mitogen-activated protein kinases (MAPKs)/transforming growth factor β1 (TGF-β1)/tumor necrosis factor pathway in atrial fibrosis, we undertook investigation of this signaling pathway in atrial fibrosis of patients with chronic AF (CAF) and rheumatic mitral valve disease. METHODS: Fifty-six rheumatic mitral valve disease patients were divided into CAF (course of AF >12 months) and sinus rhythm (SR) groups. Left atrial appendage tissue was collected during heart surgery, and pathological examination was done to evaluate atrial fibrosis. Protein and mRNA expression of TGF-β1, TRAF6 and connective tissue growth factor (CTGF) and protein expression of phosphorylated MAPKs and TGF-β-activated kinase 1 (TAK1) were measured. RESULTS: Histological examination revealed that the severity of atrial fibrosis in CAF patients was significantly higher, mRNA and protein expression of TGF-β1, TRAF6 and CTGF in CAF were significantly increased, and the protein expression of phosphorylated MAPKs and TAK1 was significantly increased in CAF compared to SR patients. CONCLUSION: The MAPKs/TGF-β1/TRAF6 signaling pathway is involved in atrial fibrosis of CAF patients, and TRAF6 may become a new target for the treatment of atrial fibrosis.
OBJECTIVE:Atrial remodeling is involved in atrial fibrillation (AF), and atrial fibrosis is an important marker of atrial remodeling. On the basis of our previous animal studies of the mitogen-activated protein kinases (MAPKs)/transforming growth factor β1 (TGF-β1)/tumor necrosis factor pathway in atrial fibrosis, we undertook investigation of this signaling pathway in atrial fibrosis of patients with chronic AF (CAF) and rheumatic mitral valve disease. METHODS: Fifty-six rheumatic mitral valve diseasepatients were divided into CAF (course of AF >12 months) and sinus rhythm (SR) groups. Left atrial appendage tissue was collected during heart surgery, and pathological examination was done to evaluate atrial fibrosis. Protein and mRNA expression of TGF-β1, TRAF6 and connective tissue growth factor (CTGF) and protein expression of phosphorylated MAPKs and TGF-β-activated kinase 1 (TAK1) were measured. RESULTS: Histological examination revealed that the severity of atrial fibrosis in CAF patients was significantly higher, mRNA and protein expression of TGF-β1, TRAF6 and CTGF in CAF were significantly increased, and the protein expression of phosphorylated MAPKs and TAK1 was significantly increased in CAF compared to SR patients. CONCLUSION: The MAPKs/TGF-β1/TRAF6 signaling pathway is involved in atrial fibrosis of CAFpatients, and TRAF6 may become a new target for the treatment of atrial fibrosis.