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Gene expression in ischemic, end-stage failing and non-failing human hearts

ABSTRACT: A goal of this study was to identify and investigate previously unrecognized components of the remodeling process in the progression to heart failure by comparing gene expression in ischemic, failing (F) to non-failing (NF) hearts. These results also were compared to the changes observed in a proteomic analysis of F and NF hearts.

ORGANISM(S): Homo sapiens

PROVIDER: GSE76701 | GEO | 2016/02/08

SECONDARY ACCESSION(S): PRJNA308420

REPOSITORIES: GEO

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Project description:Mechanical unloading by ventricular assist devices (VAD) leads to significant gene-expression changes often summarized as reverse remodeling. However, little is known on individual transcriptome changes during VAD-support and its relationship to non-failing hearts (NF). In addition no data are available for the transcriptome regulation during non-pulsatile VAD-support. Therefore we analysed the gene-expression patterns of 30 paired samples from VAD-supported (including 8 non-pulsatile VADs) and 8 non-failing control hearts (NF) using the first total human genome-array available. Transmural myocardial samples were collected for RNA-isolation. RNA was isolated by commercial methods and processed according to chip-manufacturer recommendations. cRNA were hybridized on Affymetrix HG-U133 Plus 2.0 arrays, providing coverage of the whole human genome Array. Data was analyzed using Microarray Analysis Suite 5.0 (Affymetrix) and clustered by Expressionist software (Genedata). 352 transcripts were differentially regulated between samples from VAD-implantation and NF, whereas 510 were significantly regulated between VAD-transplantation and NF (paired t-test p<0.001, fold change >=1.6). Remarkably, only a minor fraction of 111 transcripts was regulated in heart failure (HF) and during VAD-support. Unsupervised hierarchical clustering of paired VAD- and NF-samples revealed separation of HF- and NF- samples, however individual differentiation of VAD-implantation and VAD-transplantation was not accomplished. Clustering of pulsatile and non-pulsatile VAD did not lead to robust separation of gene expression patterns. During VAD-support myocardial gene expression changes do not indicate reversal of the HF-phenotype, but reveal a distinct HF-related pattern. Transcriptome analysis of pulsatile and non-pulsatile VAD-supported hearts did not provide evidence for a pump-mode specific transcriptome pattern. Microarrays were used to elucidate the differences between non-failing control hearts and those, suffering from end-stage heart failure pre and post mechanical unloading.

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Gene expression in ischemic, end-stage failing and non-failing human hearts

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