title: Gene expression profile associated with chronic atrial fibrillation and underlying valvular heart disease in man.
abstract: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans. The pathophysiology of AF involves electrical, structural and contractile remodeling, which is associated with changes in cardiac gene expression. Previous studies of gene-expression changes in clinical AF have mostly been limited to a small number of candidate genes and have not all been well controlled for underlying heart disease. The present study assessed AF-related gene-expression changes in valve-disease patients with microarrays representing the cardiac transcriptome. Right atrial appendages from 11 patients with chronic AF and underlying valvular heart disease (AF-VHD) and seven patients in sinus rhythm with VHD (SR-VHD) were individually compared to an age-matched sinus-rhythm control group (SR-CTRL, 11 patients) using cardiac-specific microarray analysis. One-class statistical analysis was used to identify genes differentially expressed between SR-VHD and SR-CTRL patients. Two-class statistical analysis was used to identify genes differentially expressed between AF-VHD and SR-VHD patients. Out of 3863 analyzed genes, 832 genes were differentially expressed between SR-VHD and SR-CTRL patients, and 169 genes were differentially expressed between AF-VHD and SR-VHD patients. Striking AF-related changes included altered expression of nine genes pointing towards the development of fibrosis (e.g. upregulation of transforming growth factor beta1), and changes in eight genes potentially related to an increased risk of thromboembolic events (e.g. upregulation of alpha2 macroglobulin). Microarray results were confirmed by quantitative PCR. Our results suggest that AF produces a characteristic profile of gene-expression changes that may be related to the pathophysiology of the arrhythmia.
authors.affiliation: L'institut du Thorax, Inserm U533, Faculté de Médecine, 1, rue Gaston Veil, 44035 Nantes, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lamirault
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gaborit
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Le Meur
authors.forename: Catherine
authors.initials: C
authors.lastname: Chevalier
authors.forename: Gilles
authors.initials: G
authors.lastname: Lande
authors.forename: Sophie
authors.initials: S
authors.lastname: Demolombe
authors.forename: Denis
authors.initials: D
authors.lastname: Escande
authors.forename: Stanley
authors.initials: S
authors.lastname: Nattel
authors.forename: Jean J
authors.initials: JJ
authors.lastname: Léger
authors.forename: Marja
authors.initials: M
authors.lastname: Steenman
mesh_terms: D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D006349:Heart Valve Diseases / Q000235:genetics*; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D000511:alpha-Macroglobulins / Q000235:genetics
chemical_list: C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000511:alpha-Macroglobulins