title: Association of left atrial endothelin-1 with atrial rhythm, size, and fibrosis in patients with structural heart disease.
abstract: BACKGROUND
  Atrial fibrillation (AF) promotes atrial remodeling and can develop secondary to heart failure or mitral valve disease. Cardiac endothelin-1 (ET-1) expression responds to wall stress and can promote myocyte hypertrophy and interstitial fibrosis. We tested the hypothesis that atrial ET-1 is elevated in AF and is associated with AF persistence.
  
  
  RESULTS
  Left atrial appendage tissue was studied from coronary artery bypass graft, valve repair, and/or Maze procedure in patients in sinus rhythm with no history of AF (SR, n=21), with history of AF but in SR at surgery (AF/SR, n=23), and in AF at surgery (AF/AF, n=32). The correlation of LA size with atrial protein and mRNA expression of ET-1 and ET-1 receptors (ETAR and ETBR) was evaluated. LA appendage ET-1 content was higher in AF/AF than in SR, but receptor levels were similar. Immunostaining revealed that ET-1 and its receptors were present both in atrial myocytes and in fibroblasts. ET-1 content was positively correlated with LA size, heart failure, AF persistence, and severity of mitral regurgitation. Multivariate analysis confirmed associations of ET-1 with AF, hypertension, and LA size. LA size was associated with ET-1 and MR severity. ET-1 mRNA levels were correlated with genes involved in cardiac dilatation, hypertrophy, and fibrosis.
  
  
  CONCLUSIONS
  Elevated atrial ET-1 content is associated with increased LA size, AF rhythm, hypertension, and heart failure. ET-1 is associated with atrial dilatation, fibrosis, and hypertrophy and probably contributes to AF persistence. Interventions that reduce atrial ET-1 expression and/or block its receptors may slow AF progression.
authors.affiliation: Department of Molecular Cardiology, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA.
authors.forename: Fadia
authors.initials: F
authors.lastname: Mayyas
authors.forename: Mark
authors.initials: M
authors.lastname: Niebauer
authors.forename: Andrew
authors.initials: A
authors.lastname: Zurick
authors.forename: John
authors.initials: J
authors.lastname: Barnard
authors.forename: A Marc
authors.initials: AM
authors.lastname: Gillinov
authors.forename: Mina K
authors.initials: MK
authors.lastname: Chung
authors.forename: David R
authors.initials: DR
authors.lastname: Van Wagoner
mesh_terms: D000368:Aged; D020517:Atrial Appendage / Q000737:chemistry* / Q000473:pathology / Q000503:physiopathology; D001281:Atrial Fibrillation / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016279:Atrial Function, Left; D006332:Cardiomegaly / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D004452:Echocardiography; D019332:Endothelin-1 / Q000032:analysis* / Q000235:genetics; D005260:Female; D005355:Fibrosis; D006331:Heart Diseases / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006333:Heart Failure / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000032:analysis; D044023:Receptor, Endothelin B / Q000032:analysis; D018570:Risk Assessment; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B