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Circ Arrhythm Electrophysiol. 2010 Aug;3(4):369-79. doi: 10.1161/CIRCEP.109.924985. Epub 2010 May 21.

Association of left atrial endothelin-1 with atrial rhythm, size, and fibrosis in patients with structural heart disease.

Author information

1
Department of Molecular Cardiology, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA.

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.

METHODS AND 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.

PMID:
20495015
PMCID:
PMC3050013
DOI:
10.1161/CIRCEP.109.924985
[Indexed for MEDLINE]
Free PMC Article

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