title: Role of tumor necrosis factor-alpha in the pathogenesis of atrial fibrillation.
abstract: BACKGROUND
  Tumor necrosis factor-alpha (TNF-α) is a pleiotropic proinflammatory cytokine and contributes to many kinds of cardiovascular diseases via its receptors (TNFR1/TNFR2). We hypothesize that TNF-α plays a role in the pathogenesis of chronic atrial fibrillation (AF).
  
  
  METHODS
  Sixty-seven consecutive patients who were scheduled to have cardiac surgery were enrolled into the study. Thirty-one patients with rheumatic heart disease (RHD) and AF were enrolled as study group (AF group). The sinus rhythm (SR) control groups consisted of 20 patients with RHD and 16 patients with coronary artery disease (CAD). Peripheral blood sample was collected before the operation. About 5 mm(3) left atrial tissue was disserted during the operation and was separated into three parts for Western blotting, real time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) analysis.
  
  
  RESULTS
  Compared with the controls (RHD SR and CAD SR), the levels of TNF-α ((14.40 ± 5.45) pg/ml vs. (4.20 ± 3.19) pg/ml vs. (2.68 ± 2.20) pg/ml, P = 0.000) and its soluble receptor 1 (sTNFR1) ((1623.9 ± 558.6) pg/ml vs. (1222.3 ± 175.6) pg/ml vs. (1387.5 ± 362.2) pg/ml, P = 0.001) in plasma were higher in patients with AF. TNF-α level had positive correlation with the left atrial diameter (LAD) (r = 0.642, P = 0.000). Western blotting analysis showed that the protein levels of TNF-α (0.618 ± 0.236 vs. 0.234 ± 0.178 vs. 0.180 ± 0.103, P = 0.000) were higher in patients with AF. The RT-PCR analysis results demonstrated that the mRNA expression of TNF-α (0.103 ± 0.047 vs. 0.031 ± 0.027 vs. 0.023 ± 0.018, P = 0.000) increased in patients with AF. IHC analysis displayed that, comparing to the SR, the expression of TNF-α (0.125 ± 0.025 vs. 0.080 ± 0.027 vs. 0.070 ± 0.023, P = 0.000) increased in the AF group. The protein level and mRNA expression of TNF-α also had positive correlation with left atrium diameter (LAD) (r = 0.415, P = 0.000 and r = 0.499, P = 0.000).
  
  
  CONCLUSIONS
  The results revealed that TNF-α elevated in the plasma and left atrial tissue and had positive correlation with LAD in patients of chronic AF. TNF-α might involve in the pathogenesis of chronic AF.
authors.affiliation: Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Deng
authors.forename: Yu-mei
authors.initials: YM
authors.lastname: Xue
authors.forename: Xian-zhang
authors.initials: XZ
authors.lastname: Zhan
authors.forename: Hong-tao
authors.initials: HT
authors.lastname: Liao
authors.forename: Hui-ming
authors.initials: HM
authors.lastname: Guo
authors.forename: Shu-lin
authors.initials: SL
authors.lastname: Wu
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood* / Q000378:metabolism*; D015153:Blotting, Western; D005260:Female; D006325:Heart Atria / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000235:genetics / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha