Role of the MAPKs/TGF-ß1/TRAF6 signaling pathway in postoperative atrial fibrillation.

ABSTRACT

OBJECTIVES: To explore the relationship between the MAPKs/TGF-ß1/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-ß1/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-ß1, TRAF6, and connective tissue growth factor (CTGF), respectively. Western blot was also used to measure the protein expression of phosphorylated MAPKs and TGF-ß-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-ß1, 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. CONCLUSION: The MAPKs/TGF-ß1/TRAF6 signaling pathway is involved in atrial fibrosis in patients with RHD, which results in the occurrence of AF after cardiac surgery.