Key result
Chronic atrial fibrillation was associated with significantly higher atrial fibrosis and increased expression of TGF-β1, TRAF6, and CTGF compared to sinus rhythm.
Observational (n=56)
The MAPKs/TGF-β1/TRAF6 signaling pathway is upregulated in patients with chronic atrial fibrillation and rheumatic mitral valve disease, suggesting TRAF6 as a potential therapeutic target for atrial fibrosis.
Should not change AF management; hypothesis-generating for TRAF6-targeted antifibrotic therapy.
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.
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Zhang et al. (2014) conducted an observational in Chronic atrial fibrillation and rheumatic mitral valve disease (n=56). Chronic atrial fibrillation vs. Sinus rhythm was evaluated on Atrial fibrosis severity and expression of TGF-β1, TRAF6, CTGF, phosphorylated MAPKs, and TAK1. Chronic atrial fibrillation was associated with significantly higher atrial fibrosis and increased expression of TGF-β1, TRAF6, and CTGF compared to sinus rhythm.
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