title: Increased expression of extracellular signal-regulated kinase and angiotensin-converting enzyme in human atria during atrial fibrillation.
abstract: OBJECTIVE
  The purpose of this study was to determine whether atrial expression of the extracellular signal-regulated kinases Erk1/Erk2 and of the angiotensin-converting enzyme (ACE) is altered in patients with atrial fibrillation (AF).
  
  
  BACKGROUND
  Recent studies have demonstrated that atrial fibrosis can provide a pathophysiologic substrate for AF. However, the molecular mechanisms responsible for the development of atrial fibrosis are unclear.
  
  
  METHODS
  Atrial tissue samples of 43 patients undergoing open heart surgery were examined. Seventeen patients had chronic persistent AF (> or =6 months; CAF), 8 patients had paroxysmal AF (PAF) and 18 patients had no history of AF. Erk expression was analyzed at the mRNA (quantitative reverse transcription polymerase chain reaction), the protein (immunoblot techniques) and atrial tissue (immunohistochemistry) levels. Erk-activating kinases (MEK1/2) and ACE were analyzed by immunoblot techniques.
  
  
  RESULTS
  Increased amounts of Erk2-mRNA were found in patients with CAF (75 +/- 20 U vs. sinus rhythm: 31 +/- 25 U; p < 0.05). Activated Erk1/Erk2 and MEK1/2 were increased to more than 150% in patients with AF compared to patients with sinus rhythm. No differences between CAF and PAF were found. The expression of ACE was three-fold increased during CAF. Amounts of activated Erk1/Erk2 were reduced in patients treated with ACE inhibitors. Patients with AF showed an increased expression of Erk1/Erk2 in interstitial cells and marked atrial fibrosis.
  
  
  CONCLUSIONS
  An ACE-dependent increase in the amounts of activated Erk1/Erk2 in atrial interstitial cells may contribute as a molecular mechanism for the development of atrial fibrosis in patients with AF. These findings may have important impact on the treatment of AF.
authors.affiliation: University Hospital Magdeburg, Department of Internal Medicine, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Goette
authors.forename: T
authors.initials: T
authors.lastname: Staack
authors.forename: C
authors.initials: C
authors.lastname: Röcken
authors.forename: M
authors.initials: M
authors.lastname: Arndt
authors.forename: J C
authors.initials: JC
authors.lastname: Geller
authors.forename: C
authors.initials: C
authors.lastname: Huth
authors.forename: S
authors.initials: S
authors.lastname: Ansorge
authors.forename: H U
authors.initials: HU
authors.lastname: Klein
authors.forename: U
authors.initials: U
authors.lastname: Lendeckel
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics* / Q000473:pathology; D004719:Endomyocardial Fibrosis / Q000235:genetics / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006325:Heart Atria / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D007703:Peptidyl-Dipeptidase A