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Cell Adhesion and Fibrosis Affect the Mechanical and Electrical Coupling Of Cardiomyocytes in Human Atrial Fibrillation
Author(s) -
Bodi Ilona,
Jessen Walter,
D'souza Karen,
Koch Sheryl,
Akhter Shahab,
Wolf Randall,
Schwartz Arnold,
Aronow Bruce
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.798.11
Subject(s) - atrial fibrillation , medicine , fibrosis , cardiology , sinus rhythm , ctgf , heart failure , myocardial fibrosis , endocrinology , receptor , growth factor
Background: Atrial fibrillation (AF) is the most common sustained arrhythmia. Long term AF leads to extensive structural remodeling with progressive contractile and electrophysiological dysfunction and system‐wide sequelae. We compared gene expression profiles of left atrial appendages from patients suffering from AF to normal atrial tissue from patients without history of AF. Methods and Results: The study consisted of three groups of patients; those with no history of AF in sinus rhythm (SR) and patients undergoing cardiac Mini‐Maze surgery for paroxysmal AF (PAF) and chronic AF (CAF). Gene expression analysis was carried out using Affymetrix microarrays and confirmed by western‐blot. Relative to SR controls, PAF and CAF samples showed statistically significant increases in the expression of genes associated with TGF‐β signaling and focal adhesion, including BMP6, CTGF, DPT, FN1, FST, JAM2, POSTN, SMAD7 and TNFAIP6. Increased expression of POSTN has also been implicated in myocyte hypertrophy in human ventricle during end‐stage heart failure. Dysregulated expression of TRDN, HDAC9, MYL2, TPM3 and TNNI3, significantly associated with calcium signaling, was only identified in patients with CAF. A key biomarker of inflammation, IFNG, was significantly upregulated between PAF and CAF. Conclusions: Our results strongly support the hypothesis that therapeutic measures designed to limit the extent of TGF‐β signaling and fibrosis such as the use of the ACEI losartan which induces regression of severe myocardial fibrosis, may be highly effective at limiting long‐term electromechanical dysfunction.