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  Expression profiling of human idiopathic dilated cardiomyopathy

Grzeskowiak, R., Witt, H., Drungowski, M., Thermann, R., Hennig, S., Perrot, A., et al. (2003). Expression profiling of human idiopathic dilated cardiomyopathy. Cardiovascular Research, 59(2), 400-411. doi:10.1016/S0008-6363(03)00426-7.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-89D2-D Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-89D3-B
Genre: Journal Article
Alternative Title : Cardiovasc. Res.

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 Creators:
Grzeskowiak, Rafal, Author
Witt, Henning1, Author
Drungowski, Mario, Author
Thermann, Rolf, Author
Hennig, Steffen2, Author              
Perrot, Andreas, Author
Osterziel, Karl J., Author
Klingbiel, Dirk1, Author
Scheid, Stefanie1, Author
Spang, Rainer3, Author              
Lehrach, Hans2, Author              
Ruiz, Patricia1, Author
Affiliations:
1Max Planck Society, ou_persistent13              
2Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
3Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433547              

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Free keywords: UniGene, cardiomyopathy, cardiac biopsy, expression profile, cDNA array
 Abstract: Objective: To investigate the global changes accompanying human dilated cardiomyopathy (DCM) we performed a large-scale expression screen using myocardial biopsies from a group of DCM patients with moderate heart failure. By hierarchical clustering and functional annotation of the deregulated genes we examined extensive changes in the cellular and molecular processes associated to DCM. Methods: The expression profiles were obtained using a whole genome covering library (UniGene RZPD1) comprising 30336 cDNA clones and amplified RNA from myocardiac biopsies from 10 DCM patients in comparison to tissue samples from four non-failing, healthy donors. Results: By setting stringent selection criteria 364 differentially expressed, sequence-verified non-redundant transcripts were identified with a false discovery rate of <0.001. Numerous genes and ESTs were identified representing previously recognised, as well as novel DCM-associated transcripts. Many of them were found to be upregulated and involved in cardiomyocyte energetics, muscle contraction or signalling. Two hundred and twenty-two deregulated transcripts were functionally annotated and hierarchically clustered providing an insight into the pathophysiology of DCM. Data was validated using the MLP-deficient mouse, in which several differentially expressed transcripts identified in the human DCM biopsies could be confirmed. Conclusions: We report the first genome-wide expression profile analysis using cardiac biopsies from DCM patients at various stages of the disease. Although there is a diversity of links between the cytoskeleton and the initiation of DCM, we speculate that genes implicated in intracellular signalling and in muscle contraction are associated with early stages of the disease. Altogether this study represents the most comprehensive and inclusive molecular portrait of human cardiomyopathy to date.

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Language(s): eng - English
 Dates: 2003-08-01
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: eDoc: 175367
ISI: 000184980500018
DOI: 10.1016/S0008-6363(03)00426-7
 Degree: -

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Title: Cardiovascular Research
  Alternative Title : Cardiovasc. Res.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 59 (2) Sequence Number: - Start / End Page: 400 - 411 Identifier: ISSN: 0008-6363