title: Proinflammatory gene expression in patients undergoing mitral valve surgery and maze ablation for atrial fibrillation.
abstract: OBJECTIVE
  It is difficult to achieve rhythm control in patients with long-standing persistent atrial fibrillation (AF). The radiofrequency maze procedure is an effective means in curing AF with a variable recurrence rate depending on patient characteristics and AF duration. In these patients, the characteristics of the atrial substrate have not been well investigated. Because the inflammatory process has been shown to be important in the pathogenesis of AF, we sought to characterize the proinflammatory gene expression in left atria obtained from patients with AF undergoing mitral valve surgery combined with the maze procedure to distinguish the changes associated with AF and its recurrence after the surgical ablation.
  
  
  METHODS
  Left atrial appendages from 35 patients receiving mitral valve surgery were used for study. Ten patients had sinus rhythm (SR) and 25 patients had persistent AF for more than 1 year and underwent the maze procedure. Among the AF patients, 13 patients remained in SR (AF-SR) and 12 patients had recurrent AF during the 1-year clinical follow-up (AF-AF). The nCounter Human Inflammation Array (NanoString Technologies, Seattle, Wash) was used for evaluating proinflammatory gene expression. Quantitative polymerase chain reaction, Western blot, and immunohistochemistry were applied for studying messenger RNA and protein expression.
  
  
  RESULTS
  Of 144 expressed proinflammatory genes, the inflammation array analysis revealed that 32 genes were differentially expressed between AF (including AF-SR and AF-AF) and SR. Thirteen genes were differentially expressed between AF-SR and AF-AF. The array and quantitative polymerase chain reaction produced parallel results in analyzing the expression of particular genes. Concordant with the gene expression difference between AF and SR patients, rapid pacing increased the expressions of SHC1, RHOA, PDGFA, and TRAF2 in HL-1 myocytes, implicating a causative effect of tachyarrhythmia on these genes. Compared with AF-SR, AF-AF expressed more intense oxidative stress, upregulations of collagen, transforming growth factor beta 1, and intranuclear nuclear factor of activated T-cells. Regression analysis showed that increased left atrial diameter was associated with the expression of RHOA and STAT1.
  
  
  CONCLUSIONS
  Differential expression profiles of proflammatory genes were presented between SR and AF and between maintained SR and recurrent AF after the maze procedure. The identified inflammatory molecules associated with AF and failed surgical ablation may provide clues for developing new potential therapeutic targets to improve AF rhythm control.
authors.affiliation: Division of Cardiac Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Feng-Chun
authors.initials: FC
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Clinical Medical Sciences, Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Gwo-Jyh
authors.initials: GJ
authors.lastname: Chang
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yu-Juei
authors.initials: YJ
authors.lastname: Hsu
authors.affiliation: School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yuan-Min
authors.initials: YM
authors.lastname: Lin
authors.affiliation: Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan.
authors.forename: Yun-Shien
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Cardiovascular Division, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Wei-Jan
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Cardiovascular Division, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Chi-Tai
authors.initials: CT
authors.lastname: Kuo
authors.affiliation: Cardiovascular Division, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: yeongshinn@cgmh.org.tw.
authors.forename: Yung-Hsin
authors.initials: YH
authors.lastname: Yeh
mesh_terms: D001281:Atrial Fibrillation / Q000150:complications / Q000235:genetics / Q000601:surgery*; D015153:Blotting, Western; D006348:Cardiac Surgical Procedures / Q000379:methods*; D017115:Catheter Ablation / Q000379:methods*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006325:Heart Atria / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008944:Mitral Valve Insufficiency / Q000150:complications / Q000235:genetics / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C066737:RHOA protein, human; D012313:RNA; D020742:rhoA GTP-Binding Protein
keywords: NFAT; atrial fibrillation; inflammation; maze