Association of left atrial endothelin-1 with atrial rhythm, size, and fibrosis in patients with structural heart disease.
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.
Mayyas
Fadia
F
Department of Molecular Cardiology, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA.
Niebauer
Mark
M
Zurick
Andrew
A
Barnard
John
J
Gillinov
A Marc
AM
Chung
Mina K
MK
Van Wagoner
David R
DR
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
D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B