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Status |
Public on May 13, 2005 |
Title |
Comparison of atrial tissue of patients with atrial fibrillation and sinus rhythm with ventricular gene expression |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
GSE2240 contains two different experimental subsets:
1) Comparison of atrial and ventricular gene expression (atrial tissue of patients with sinus rhythm vs. human left ventricular non-failing myocardium)
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 (Barth AS et al., Eur J Physiol, 2005).
2) Comparison of atrial gene expression in patients with permanent atrial fibrillation and sinus rhythm.
Atrial fibrillation is associated with increased expression of ventricular myosin isoforms in atrial myocardium, regarded as part of a dedifferentiation process. Whether re-expression of ventricular isoforms in atrial fibrillation is restricted to transcripts encoding for contractile proteins is unknown. Therefore, this study compares atrial mRNA expression in patients with permanent atrial fibrillation to atrial mRNA expression of patients with sinus rhythm as well as to ventricular gene expression using Affymetrix U133 arrays. In atrial myocardium, we identified 1.434 genes deregulated in atrial fibrillation, the majority of which, including key elements of calcium-dependent signaling pathways, displayed down-regulation. Functional classification based on Gene Ontology provided the specific gene sets of the interdependent processes of structural, contractile and electrophysiological remodeling. In addition, we demonstrate for the first time a prominent up-regulation of transcripts involved in metabolic activities, suggesting an adaptive response to an increased metabolic demand in fibrillating atrial myocardium. Ventricular-predominant genes were five times more likely to be up-regulated in atrial fibrillation (174 genes up-regulated, 35 genes down-regulated), while atrial-specific transcripts were predominantly down-regulated (56 genes up-regulated, 564 genes down-regulated). Overall, in atrial myocardium, functional classes of genes characteristic of ventricular myocardium were found to be up-regulated (e.g. metabolic processes) while functional classes predominantly expressed in atrial myocardium were down-regulated in atrial fibrillation (e.g. signal transduction and cell communication). Therefore, dedifferentiation with adoption of a ventricular-like signature is a general feature of the fibrillating atrium, uncovering the transcriptional response pattern in pmAF (Barth AS et al., Circ Res, 2005). Keywords = human myocardium Keywords = atrial fibrillation Keywords = sinus rhythm Keywords = left ventricular gene expression Keywords: other
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Contributor(s) |
Barth AS, Merk S, Arnoldi E, Zwermann L, Kloos P, Gebauer M, Steinmeyer K, Bleich M, Kääb S, Hinterseer M, Kartmann H, Kreuzer E, Dugas M, Steinbeck G, Näbauer M |
Citation(s) |
15877233, 15817885 |
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Submission date |
Feb 03, 2005 |
Last update date |
Aug 10, 2018 |
Contact name |
Andreas S. Barth |
E-mail(s) |
[email protected]
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Phone |
0049-(0)89-7095-0
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Organization name |
University of Munich (LMU), Grosshadern
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Department |
Department of Cardiology
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Street address |
Marchioninistr. 15
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City |
Munich |
ZIP/Postal code |
81377 |
Country |
Germany |
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Platforms (2) |
GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
GPL97 |
[HG-U133B] Affymetrix Human Genome U133B Array |
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Samples (70)
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GSM40980 |
atrial myocardium, atrial fibrillation 1 |
GSM40981 |
atrial myocardium, atrial fibrillation 2 |
GSM40982 |
atrial myocardium, atrial fibrillation 3 |
GSM40983 |
atrial myocardium, atrial fibrillation 4 |
GSM40984 |
atrial myocardium, atrial fibrillation 5 |
GSM40985 |
atrial myocardium, atrial fibrillation 6 |
GSM40986 |
atrial myocardium, atrial fibrillation 7 |
GSM40987 |
atrial myocardium, atrial fibrillation 8 |
GSM40988 |
atrial myocardium, atrial fibrillation 9 |
GSM40989 |
atrial myocardium, atrial fibrillation 10 |
GSM40990 |
atrial myocardium, sinus rhythm 1 |
GSM40991 |
atrial myocardium, sinus rhythm 2 |
GSM40992 |
atrial myocardium, sinus rhythm 3 |
GSM40993 |
atrial myocardium, sinus rhythm 4 |
GSM40994 |
atrial myocardium, sinus rhythm 5 |
GSM40995 |
atrial myocardium, sinus rhythm 6 |
GSM40996 |
atrial myocardium, sinus rhythm 7 |
GSM40997 |
atrial myocardium, sinus rhythm 8 |
GSM40998 |
atrial myocardium, sinus rhythm 9 |
GSM40999 |
atrial myocardium, sinus rhythm 10 |
GSM41000 |
atrial myocardium, sinus rhythm 11 |
GSM41001 |
atrial myocardium, sinus rhythm 12 |
GSM41002 |
atrial myocardium, sinus rhythm 13 |
GSM41003 |
atrial myocardium, sinus rhythm 14 |
GSM41004 |
atrial myocardium, sinus rhythm 15 |
GSM41005 |
atrial myocardium, sinus rhythm 16 |
GSM41006 |
atrial myocardium, sinus rhythm 17 |
GSM41007 |
atrial myocardium, sinus rhythm 18 |
GSM41008 |
atrial myocardium, sinus rhythm 19 |
GSM41009 |
atrial myocardium, sinus rhythm 20 |
GSM41010 |
left ventricular myocardium, non-failing 1 |
GSM41011 |
left ventricular myocardium, non-failing 2 |
GSM41012 |
left ventricular myocardium, non-failing 3 |
GSM41013 |
left ventricular myocardium, non-failing 4 |
GSM41014 |
left ventricular myocardium, non-failing 5 |
GSM41085 |
atrial myocardium, atrial fibrillation 1B |
GSM41086 |
atrial myocardium, atrial fibrillation 2B |
GSM41087 |
atrial myocardium, atrial fibrillation 3B |
GSM41088 |
atrial myocardium, atrial fibrillation 4B |
GSM41089 |
atrial myocardium, atrial fibrillation 5B |
GSM41090 |
atrial myocardium, atrial fibrillation 6B |
GSM41091 |
atrial myocardium, atrial fibrillation 7B |
GSM41092 |
atrial myocardium, atrial fibrillation 8B |
GSM41093 |
atrial myocardium, atrial fibrillation 9B |
GSM41094 |
atrial myocardium, atrial fibrillation 10B |
GSM41095 |
atrial myocardium, sinus rhythm 1B |
GSM41096 |
atrial myocardium, sinus rhythm 2B |
GSM41097 |
atrial myocardium, sinus rhythm 3B |
GSM41098 |
atrial myocardium, sinus rhythm 4B |
GSM41099 |
atrial myocardium, sinus rhythm 5B |
GSM41100 |
atrial myocardium, sinus rhythm 6B |
GSM41101 |
atrial myocardium, sinus rhythm 7B |
GSM41102 |
atrial myocardium, sinus rhythm 8B |
GSM41103 |
atrial myocardium, sinus rhythm 9B |
GSM41104 |
atrial myocardium, sinus rhythm 10B |
GSM41105 |
atrial myocardium, sinus rhythm 11B |
GSM41106 |
atrial myocardium, sinus rhythm 12B |
GSM41107 |
atrial myocardium, sinus rhythm 13B |
GSM41108 |
atrial myocardium, sinus rhythm 14B |
GSM41109 |
atrial myocardium, sinus rhythm 15B |
GSM41110 |
atrial myocardium, sinus rhythm 16B |
GSM41111 |
atrial myocardium, sinus rhythm 17B |
GSM41112 |
atrial myocardium, sinus rhythm 18B |
GSM41113 |
atrial myocardium, sinus rhythm 19B |
GSM41114 |
atrial myocardium, sinus rhythm 20B |
GSM41115 |
left ventricular myocardium, non-failing 1B |
GSM41116 |
left ventricular myocardium, non-failing 2B |
GSM41117 |
left ventricular myocardium, non-failing 3B |
GSM41118 |
left ventricular myocardium, non-failing 4B |
GSM41119 |
left ventricular myocardium, non-failing 5B |
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Relations |
BioProject |
PRJNA91505 |
Supplementary file |
Size |
Download |
File type/resource |
GSE2240_RAW.tar |
251.1 Mb |
(http)(custom) |
TAR (of CEL) |
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