title: Endothelin system in human persistent and paroxysmal atrial fibrillation.
abstract: BACKGROUND
  Activation of the endothelin system is an important compensatory mechanism that is activated during left ventricular dysfunction. Whether this system plays a role at the atrial level during atrial fibrillation (AF) has not been examined in detail. The purpose of this study was to investigate mRNA and protein expression levels of the endothelin system in AF patients with and without concomitant underlying valve disease.
  
  
  RESULTS
  Right atrial appendages of 36 patients with either paroxysmal or persistent AF were compared with 36 controls in sinus rhythm. The mRNA amounts of pro-endothelin-1 (pro-ET-1), endothelin receptor A (ET-A), and endothelin receptor B (ET-B) were studied by semiquantitative polymerase chain reaction. Protein amounts of the receptors were investigated by slot-blot analysis. mRNA amounts of pro-ET-1 were increased (+40%; P = 0.002) only in AF patients with underlying valve disease. ET-A and ET-B receptor protein amounts were significantly reduced in patients with paroxysmal AF (-39% and -47%, respectively) and persistent AF with underlying valve disease (-28% and -30%, respectively) and in persistent AF without valve disease (-20% and -40%, respectively). ET-A mRNA expression was unaltered in paroxysmal and persistent AF, whereas ET-B mRNA was reduced by 30% in persistent AF with (P < 0.001) or without (P = 0.04) valve disease, but unchanged in paroxysmal AF.
  
  
  CONCLUSIONS
  Substantial changes in gene expression of the endothelin system were observed in human atria during AF, especially in the presence of underlying valve disease. Alterations in endothelin expression associated with AF could play a role in the pathophysiology of AF and the progression of underlying heart disease.
authors.affiliation: Department of Cardiology, Thoraxcenter University Hospital Groningen, The Netherlands. B.J.J.M.Brundel@med.rug.nl
authors.forename: B J
authors.initials: BJ
authors.lastname: Brundel
authors.forename: I C
authors.initials: IC
authors.lastname: Van Gelder
authors.forename: A E
authors.initials: AE
authors.lastname: Tuinenburg
authors.forename: M
authors.initials: M
authors.lastname: Wietses
authors.forename: D J
authors.initials: DJ
authors.lastname: Van Veldhuisen
authors.forename: W H
authors.initials: WH
authors.lastname: Van Gilst
authors.forename: H J
authors.initials: HJ
authors.lastname: Crijns
authors.forename: R H
authors.initials: RH
authors.lastname: Henning
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000503:physiopathology*; D019332:Endothelin-1; D016232:Endothelins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006325:Heart Atria; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D020033:Protein Isoforms; D011498:Protein Precursors; D012333:RNA, Messenger; C093240:proendothelin 1; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases