title: Left atrial transcriptional changes associated with atrial fibrillation susceptibility and persistence.
abstract: BACKGROUND
  Prior transcriptional studies of atrial fibrillation (AF) have been limited to specific transcripts, animal models, chronic AF, right atria, or small samples. We sought to characterize the left atrial transcriptome in human AF to distinguish changes related to AF susceptibility and persistence.
  
  
  RESULTS
  Left atrial appendages from 239 patients stratified by coronary artery disease, valve disease, and AF history (no history of AF, AF history in sinus rhythm at surgery, and AF history in AF at surgery) were selected for genome-wide mRNA microarray profiling. Transcripts were examined for differential expression with AF phenotype group. Enrichment in differentially expressed genes was examined in 3 gene set collections: a transcription factor collection, defined by shared conserved cis-regulatory motifs, a miRNA collection, defined by shared 3' untranslated region motifs, and a molecular function collection, defined by shared Gene Ontology molecular function. AF susceptibility was associated with decreased expression of the targets of CREB/ATF family, heat-shock factor 1, ATF6, SRF, and E2F1 transcription factors. Persistent AF activity was associated with decreased expression in genes and gene sets related to ion channel function consistent with reported functional changes.
  
  
  CONCLUSIONS
  AF susceptibility was associated with decreased expression of targets of several transcription factors related to inflammation, oxidation, and cellular stress responses. In contrast, changes in ion channel expression were associated with AF activity but were limited in AF susceptibility. Our results suggest that significant transcriptional remodeling marks susceptibility to AF, whereas remodeling of ion channel expression occurs later in the progression or as a consequence of AF.
authors.affiliation: From the Department of Medicine, University of Chicago, IL (A.D.); Department of Quantitative Health Sciences (J.B; H.S.), Department of Molecular Cardiology (L.C., D.R.V.W., M.K.C.), and Department of Cellular and Molecular Medicine, Cleveland Clinic (J.D.S.), Lerner Research Institute, OH; Department of Cardiovascular Medicine (D.N., C.M., J.D.S., M.K.C.) and Department of Cardiovascular Medicine and Thoracic and Cardiovascular Surgery (G.P., D.J., E.R., A.M.G., K.M.), Heart and Vascular Institute, Cleveland, OH; and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (C.M., J.D.S., D.R.V.W., M.K.C.).
authors.forename: Amrish
authors.initials: A
authors.lastname: Deshmukh
authors.affiliation: From the Department of Medicine, University of Chicago, IL (A.D.); Department of Quantitative Health Sciences (J.B; H.S.), Department of Molecular Cardiology (L.C., D.R.V.W., M.K.C.), and Department of Cellular and Molecular Medicine, Cleveland Clinic (J.D.S.), Lerner Research Institute, OH; Department of Cardiovascular Medicine (D.N., C.M., J.D.S., M.K.C.) and Department of Cardiovascular Medicine and Thoracic and Cardiovascular Surgery (G.P., D.J., E.R., A.M.G., K.M.), Heart and Vascular Institute, Cleveland, OH; and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (C.M., J.D.S., D.R.V.W., M.K.C.).
authors.forename: John
authors.initials: J
authors.lastname: Barnard
authors.affiliation: From the Department of Medicine, University of Chicago, IL (A.D.); Department of Quantitative Health Sciences (J.B; H.S.), Department of Molecular Cardiology (L.C., D.R.V.W., M.K.C.), and Department of Cellular and Molecular Medicine, Cleveland Clinic (J.D.S.), Lerner Research Institute, OH; Department of Cardiovascular Medicine (D.N., C.M., J.D.S., M.K.C.) and Department of Cardiovascular Medicine and Thoracic and Cardiovascular Surgery (G.P., D.J., E.R., A.M.G., K.M.), Heart and Vascular Institute, Cleveland, OH; and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (C.M., J.D.S., D.R.V.W., M.K.C.).
authors.forename: Han
authors.initials: H
authors.lastname: Sun
authors.affiliation: From the Department of Medicine, University of Chicago, IL (A.D.); Department of Quantitative Health Sciences (J.B; H.S.), Department of Molecular Cardiology (L.C., D.R.V.W., M.K.C.), and Department of Cellular and Molecular Medicine, Cleveland Clinic (J.D.S.), Lerner Research Institute, OH; Department of Cardiovascular Medicine (D.N., C.M., J.D.S., M.K.C.) and Department of Cardiovascular Medicine and Thoracic and Cardiovascular Surgery (G.P., D.J., E.R., A.M.G., K.M.), Heart and Vascular Institute, Cleveland, OH; and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (C.M., J.D.S., D.R.V.W., M.K.C.).
authors.forename: David
authors.initials: D
authors.lastname: Newton
authors.affiliation: From the Department of Medicine, University of Chicago, IL (A.D.); Department of Quantitative Health Sciences (J.B; H.S.), Department of Molecular Cardiology (L.C., D.R.V.W., M.K.C.), and Department of Cellular and Molecular Medicine, Cleveland Clinic (J.D.S.), Lerner Research Institute, OH; Department of Cardiovascular Medicine (D.N., C.M., J.D.S., M.K.C.) and Department of Cardiovascular Medicine and Thoracic and Cardiovascular Surgery (G.P., D.J., E.R., A.M.G., K.M.), Heart and Vascular Institute, Cleveland, OH; and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (C.M., J.D.S., D.R.V.W., M.K.C.).
authors.forename: Laurie
authors.initials: L
authors.lastname: Castel
authors.affiliation: From the Department of Medicine, University of Chicago, IL (A.D.); Department of Quantitative Health Sciences (J.B; H.S.), Department of Molecular Cardiology (L.C., D.R.V.W., M.K.C.), and Department of Cellular and Molecular Medicine, Cleveland Clinic (J.D.S.), Lerner Research Institute, OH; Department of Cardiovascular Medicine (D.N., C.M., J.D.S., M.K.C.) and Department of Cardiovascular Medicine and Thoracic and Cardiovascular Surgery (G.P., D.J., E.R., A.M.G., K.M.), Heart and Vascular Institute, Cleveland, OH; and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (C.M., J.D.S., D.R.V.W., M.K.C.).
authors.forename: Gosta
authors.initials: G
authors.lastname: Pettersson
authors.affiliation: From the Department of Medicine, University of Chicago, IL (A.D.); Department of Quantitative Health Sciences (J.B; H.S.), Department of Molecular Cardiology (L.C., D.R.V.W., M.K.C.), and Department of Cellular and Molecular Medicine, Cleveland Clinic (J.D.S.), Lerner Research Institute, OH; Department of Cardiovascular Medicine (D.N., C.M., J.D.S., M.K.C.) and Department of Cardiovascular Medicine and Thoracic and Cardiovascular Surgery (G.P., D.J., E.R., A.M.G., K.M.), Heart and Vascular Institute, Cleveland, OH; and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (C.M., J.D.S., D.R.V.W., M.K.C.).
authors.forename: Douglas
authors.initials: D
authors.lastname: Johnston
authors.affiliation: From the Department of Medicine, University of Chicago, IL (A.D.); Department of Quantitative Health Sciences (J.B; H.S.), Department of Molecular Cardiology (L.C., D.R.V.W., M.K.C.), and Department of Cellular and Molecular Medicine, Cleveland Clinic (J.D.S.), Lerner Research Institute, OH; Department of Cardiovascular Medicine (D.N., C.M., J.D.S., M.K.C.) and Department of Cardiovascular Medicine and Thoracic and Cardiovascular Surgery (G.P., D.J., E.R., A.M.G., K.M.), Heart and Vascular Institute, Cleveland, OH; and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (C.M., J.D.S., D.R.V.W., M.K.C.).
authors.forename: Eric
authors.initials: E
authors.lastname: Roselli
authors.affiliation: From the Department of Medicine, University of Chicago, IL (A.D.); Department of Quantitative Health Sciences (J.B; H.S.), Department of Molecular Cardiology (L.C., D.R.V.W., M.K.C.), and Department of Cellular and Molecular Medicine, Cleveland Clinic (J.D.S.), Lerner Research Institute, OH; Department of Cardiovascular Medicine (D.N., C.M., J.D.S., M.K.C.) and Department of Cardiovascular Medicine and Thoracic and Cardiovascular Surgery (G.P., D.J., E.R., A.M.G., K.M.), Heart and Vascular Institute, Cleveland, OH; and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (C.M., J.D.S., D.R.V.W., M.K.C.).
authors.forename: A Marc
authors.initials: AM
authors.lastname: Gillinov
authors.affiliation: From the Department of Medicine, University of Chicago, IL (A.D.); Department of Quantitative Health Sciences (J.B; H.S.), Department of Molecular Cardiology (L.C., D.R.V.W., M.K.C.), and Department of Cellular and Molecular Medicine, Cleveland Clinic (J.D.S.), Lerner Research Institute, OH; Department of Cardiovascular Medicine (D.N., C.M., J.D.S., M.K.C.) and Department of Cardiovascular Medicine and Thoracic and Cardiovascular Surgery (G.P., D.J., E.R., A.M.G., K.M.), Heart and Vascular Institute, Cleveland, OH; and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (C.M., J.D.S., D.R.V.W., M.K.C.).
authors.forename: Kenneth
authors.initials: K
authors.lastname: McCurry
authors.affiliation: From the Department of Medicine, University of Chicago, IL (A.D.); Department of Quantitative Health Sciences (J.B; H.S.), Department of Molecular Cardiology (L.C., D.R.V.W., M.K.C.), and Department of Cellular and Molecular Medicine, Cleveland Clinic (J.D.S.), Lerner Research Institute, OH; Department of Cardiovascular Medicine (D.N., C.M., J.D.S., M.K.C.) and Department of Cardiovascular Medicine and Thoracic and Cardiovascular Surgery (G.P., D.J., E.R., A.M.G., K.M.), Heart and Vascular Institute, Cleveland, OH; and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (C.M., J.D.S., D.R.V.W., M.K.C.).
authors.forename: Christine
authors.initials: C
authors.lastname: Moravec
authors.affiliation: From the Department of Medicine, University of Chicago, IL (A.D.); Department of Quantitative Health Sciences (J.B; H.S.), Department of Molecular Cardiology (L.C., D.R.V.W., M.K.C.), and Department of Cellular and Molecular Medicine, Cleveland Clinic (J.D.S.), Lerner Research Institute, OH; Department of Cardiovascular Medicine (D.N., C.M., J.D.S., M.K.C.) and Department of Cardiovascular Medicine and Thoracic and Cardiovascular Surgery (G.P., D.J., E.R., A.M.G., K.M.), Heart and Vascular Institute, Cleveland, OH; and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (C.M., J.D.S., D.R.V.W., M.K.C.).
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Smith
authors.affiliation: From the Department of Medicine, University of Chicago, IL (A.D.); Department of Quantitative Health Sciences (J.B; H.S.), Department of Molecular Cardiology (L.C., D.R.V.W., M.K.C.), and Department of Cellular and Molecular Medicine, Cleveland Clinic (J.D.S.), Lerner Research Institute, OH; Department of Cardiovascular Medicine (D.N., C.M., J.D.S., M.K.C.) and Department of Cardiovascular Medicine and Thoracic and Cardiovascular Surgery (G.P., D.J., E.R., A.M.G., K.M.), Heart and Vascular Institute, Cleveland, OH; and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (C.M., J.D.S., D.R.V.W., M.K.C.).
authors.forename: David R
authors.initials: DR
authors.lastname: Van Wagoner
authors.affiliation: From the Department of Medicine, University of Chicago, IL (A.D.); Department of Quantitative Health Sciences (J.B; H.S.), Department of Molecular Cardiology (L.C., D.R.V.W., M.K.C.), and Department of Cellular and Molecular Medicine, Cleveland Clinic (J.D.S.), Lerner Research Institute, OH; Department of Cardiovascular Medicine (D.N., C.M., J.D.S., M.K.C.) and Department of Cardiovascular Medicine and Thoracic and Cardiovascular Surgery (G.P., D.J., E.R., A.M.G., K.M.), Heart and Vascular Institute, Cleveland, OH; and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, OH (C.M., J.D.S., D.R.V.W., M.K.C.). chungm@ccf.org.
authors.forename: Mina K
authors.initials: MK
authors.lastname: Chung
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D020517:Atrial Appendage / Q000737:chemistry* / Q000601:surgery; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D005819:Genetic Markers; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors
keywords: ATF transcription; atrial fibrillation; transcriptome