Global gene expression in human myocardium-oligonucleotide microarray analysis of regional diversity and transcriptional regulation in heart failure.
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.
Kääb
Stefan
S
Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Grosshadern, Marchioninistrasse 15, 81377 Munich, Germany. Stefan.Kaab@med.uni-muenchen.de
Barth
Andreas S
AS
Margerie
Daniel
D
Dugas
Martin
M
Gebauer
Mathias
M
Zwermann
Ludwig
L
Merk
Sylvia
S
Pfeufer
Arne
A
Steinmeyer
Klaus
K
Bleich
Markus
M
Kreuzer
Eckart
E
Steinbeck
Gerhard
G
Näbauer
Michael
M
D000328:Adult; D002303:Cardiac Output, Low / Q000235:genetics* / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006325:Heart Atria / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000235:genetics* / Q000378:metabolism; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000235:genetics; D014158:Transcription, Genetic; D015854:Up-Regulation
D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain