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Global gene expression in human myocardium—oligonucleotide microarray analysis of regional diversity and transcriptional regulation in heart failure

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Abstract

To obtain region- and disease-specific transcription profiles of human myocardial tissue, we explored mRNA expression from all four chambers of eight explanted failing [idiopathic dilated cardiomyopathy (DCM), n=5; ischemic cardiomyopathy (ICM), n=3], and five non-failing hearts using high-density oligonucleotide arrays (Affymetrix U95Av2). We performed pair-wise comparisons of gene expression in the categories (1) atria versus ventricles, (2) disease-regulated genes in atria and (3) disease-regulated genes in ventricles. In the 51 heart samples examined, 549 genes showed divergent distribution between atria and ventricles (272 genes with higher expression in atria, 277 genes with higher expression in ventricles). Two hundred and eighty-eight genes were differentially expressed in failing myocardium compared to non-failing hearts (19 genes regulated in atria and ventricles, 172 regulated in atria only, 97 genes regulated in ventricles only). For disease-regulated genes, down-regulation was 4.5-times more common than up-regulation. Functional classification according to Gene Ontology identified specific biological patterns for differentially expressed genes. Eleven genes were validated by RT-PCR showing a good correlation with the microarray data. Our goal was to determine a gene expression fingerprint of the heart, accounting for region- and disease-specific aspects. Recognizing common gene expression patterns in heart failure will significantly contribute to the understanding of heart failure and may eventually lead to the development of pathway-specific therapies.

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Abbreviations

CMP :

Cardiomyopathy

DCM :

Idiopathic dilated cardiomyopathy

ICM :

Ischemic cardiomyopathy

LA :

Left atrium

LV :

Left ventricle

NF :

Non-failing

RA :

Right atrium

RV :

Right ventricle

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Acknowledgements

This work was funded by a grant of the Bundesministerium für Bildung und Forschung (BMBF-grant 01GS0109; S.K., M.N.) supporting the German National Genome Research Network (NGFN) and an institutional grant (FöFoLe; A.S.B.). The data presented here were generated and analyzed in the framework of a research collaboration with Aventis Pharma Deutschland GmbH.

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Authors and Affiliations

  1. Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Grosshadern, Marchioninistrasse 15, 81377 , Munich, Germany

    Stefan Kääb, Andreas S. Barth, Ludwig Zwermann, Gerhard Steinbeck & Michael Näbauer

  2. Aventis Pharma, Frankfurt a. Main, Germany

    Daniel Margerie, Mathias Gebauer, Klaus Steinmeyer & Markus Bleich

  3. Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie (IBE), Klinikum der Universität München, LMU Munich, Grosshadern, Germany

    Martin Dugas & Sylvia Merk

  4. Institut für Humangenetik, Technische Universität München und GSF Forschungszentrum, Neuherberg, Germany

    Arne Pfeufer

  5. Herzchirurgische Klinik und Poliklinik, Klinikum der Universität München, LMU Munich, Grosshadern, Germany

    Eckart Kreuzer

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  1. Stefan Kääb
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Correspondence to Stefan Kääb or Andreas S. Barth.

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S. Kääb and A.S. Barth contributed equally

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Kääb, S., Barth, A.S., Margerie, D. et al. Global gene expression in human myocardium—oligonucleotide microarray analysis of regional diversity and transcriptional regulation in heart failure. J Mol Med 82, 308–316 (2004). https://doi.org/10.1007/s00109-004-0527-2

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  • DOI: https://doi.org/10.1007/s00109-004-0527-2

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