Role of the MAPKs/TGF-β1/TRAF6 signaling pathway in atrial fibrosis of patients with chronic atrial fibrillation and rheumatic mitral valve disease.
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.


CONCLUSIONS
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.
Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, PR China.
Daoliang
D
Zhang
Xu
X
Liu
Xiaoqing
X
Chen
Jun
J
Gu
Feng
F
Li
Wei
W
Zhang
Yue
Y
Zheng
D001281:Atrial Fibrillation / Q000209:etiology*; D064752:Atrial Remodeling / Q000502:physiology; D002908:Chronic Disease; D005260:Female; D005355:Fibrosis / Q000209:etiology; D006325:Heart Atria / Q000473:pathology; D006349:Heart Valve Diseases / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008943:Mitral Valve; D012214:Rheumatic Heart Disease / Q000209:etiology*; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D048029:TNF Receptor-Associated Factor 6; D053773:Transforming Growth Factor beta1; D020928:Mitogen-Activated Protein Kinases