Role of the MAPKs/TGF-β1/TRAF6 signaling pathway in postoperative atrial fibrillation.
OBJECTIVE
To explore the relationship between the MAPKs/TGF-β1/TRAF6 signaling pathway and atrial fibrosis in patients with rheumatic heart disease (RHD) and its role in atrial fibrillation (AF) after cardiac surgery on the basis of our previous animal study of the MAPKs/TGF-β1/TRAF6 signaling pathway in atrial fibrosis.


METHODS
A total of 57 patients with RHD without a history of AF consented to left atrial biopsy. Histopathology quantified the percentage of fibrosis, and real-time PCR and western blot assessed the mRNA and protein expression of TGF-β1, TRAF6, and connective tissue growth factor (CTGF), respectively. Western blot was also used to measure the protein expression of phosphorylated MAPKs and TGF-β-activated kinase 1 (TAK1). Serum angiotensin II (Ang II) levels were assayed using enzyme-linked immunosorbent assay (ELISA).


RESULTS
Eighteen patients developed AF, whereas 39 remained in sinus rhythm (SR). The severity of atrial fibrosis was significantly higher in patients who developed AF versus those who remained in SR; the mRNA and protein expression of TGF-β1, TRAF6 and CTGF were significantly higher in patients with AF. The protein expression of phosphorylated MAPKs and TAK1 was significantly increased in patients who developed AF compared with the patients who remained in SR. Serum Ang II levels were significantly higher in patients who developed AF versus those who remained in SR.


CONCLUSIONS
The MAPKs/TGF-β1/TRAF6 signaling pathway is involved in atrial fibrosis in patients with RHD, which results in the occurrence of AF after cardiac surgery.
Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.
Daoliang
D
Zhang
Department of Cardiology, Shanghai First People's Hospital, Shanghai, People's Republic of China.
Xiaoqing
X
Chen
Department of Cardiology, Shanghai Xinhua Hospital, Shanghai, People's Republic of China.
Qian
Q
Wang
Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.
Shaohui
S
Wu
Department of Cardiac Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.
Yue
Y
Zheng
Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.
Xu
X
Liu
D000804:Angiotensin II / Q000097:blood; D020517:Atrial Appendage / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D005355:Fibrosis / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012214:Rheumatic Heart Disease / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D012720:Severity of Illness Index; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D000099151:MAP Kinase Kinase Kinase 7
D000804:Angiotensin II; D055513:Connective Tissue Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D012333:RNA, Messenger; D048029:TNF Receptor-Associated Factor 6; D053773:Transforming Growth Factor beta1; D000099151:MAP Kinase Kinase Kinase 7; C508960:TGFB1 protein, human; C000604754:Tifab protein, human