Functional profiling of human atrial and ventricular gene expression
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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.
KeywordsFunctional genomics Myocardium Atrium Ventricle Signal transduction Contraction
The authors thank Prof. B. Reichart and his colleagues for providing myocardial tissue specimens. Special thanks are due to H. Kartmann for excellent technical assistance with RT-PCR experiments. This study was supported partly by a grant of the Bundesministerium für Bildung und Forschung (BMBF-grant 01GS0109; S.K., A.P., M.N., G.S.) supporting the German National Genome Research Network (NGFN) and a grant from the scientific editorial board of the Münchner Medizinische Wochenschrift (A.S.B.). Data was generated and analysed in the framework of a research collaboration with Aventis Pharma Deutschland GmbH.
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