title: Functional profiling of human atrial and ventricular gene expression.
abstract: The purpose of our investigation was to identify the transcriptional basis for ultrastructural and functional specialization of human atria and ventricles. Using exploratory microarray analysis (Affymetrix U133A+B), we detected 11,740 transcripts expressed in human heart, representing the most comprehensive report of the human myocardial transcriptome to date. Variation in gene expression between atria and ventricles accounted for the largest differences in this data set, as 3.300 and 2.974 transcripts showed higher expression in atria and ventricles, respectively. Functional classification based on Gene Ontology identified chamber-specific patterns of gene expression and provided molecular insights into the regional specialization of cardiomyocytes, correlating important functional pathways to transcriptional activity: Ventricular myocytes preferentially express genes satisfying contractile and energetic requirements, while atrial myocytes exhibit specific transcriptional activities related to neurohumoral function. In addition, several pro-fibrotic and apoptotic pathways were concentrated in atrial myocardium, substantiating the higher susceptibility of atria to programmed cell death and extracellular matrix remodelling observed in human and experimental animal models of heart failure. Differences in transcriptional profiles of atrial and ventricular myocardium thus provide molecular insights into myocardial cell diversity and distinct region-specific adaptations to physiological and pathophysiological conditions. Moreover, as major functional classes of atrial- and ventricular-specific transcripts were common to human and murine myocardium, an evolutionarily conserved chamber-specific expression pattern in mammalian myocardium is suggested.
authors.affiliation: Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-University, Marchioninistrasse 15, 81377, Munich, Germany. andreas.barth@med.uni-muenchen.de
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Barth
authors.forename: Sylvia
authors.initials: S
authors.lastname: Merk
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Arnoldi
authors.forename: Ludwig
authors.initials: L
authors.lastname: Zwermann
authors.forename: Patrick
authors.initials: P
authors.lastname: Kloos
authors.forename: Mathias
authors.initials: M
authors.lastname: Gebauer
authors.forename: Klaus
authors.initials: K
authors.lastname: Steinmeyer
authors.forename: Markus
authors.initials: M
authors.lastname: Bleich
authors.forename: Stefan
authors.initials: S
authors.lastname: Kääb
authors.forename: Arne
authors.initials: A
authors.lastname: Pfeufer
authors.forename: Peter
authors.initials: P
authors.lastname: Uberfuhr
authors.forename: Martin
authors.initials: M
authors.lastname: Dugas
authors.forename: Gerhard
authors.initials: G
authors.lastname: Steinbeck
authors.forename: Michael
authors.initials: M
authors.lastname: Nabauer
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling / Q000379:methods*; D006325:Heart Atria / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism*; D006801:Humans; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic