title: Global gene expression analysis in nonfailing and failing myocardium pre- and postpulsatile and nonpulsatile ventricular assist device support.
abstract: 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 nonfailing hearts (NF). In addition no data are available for the transcriptome regulation during nonpulsatile VAD support. Therefore we analyzed the gene expression patterns of 30 paired samples from VAD-supported (including 8 nonpulsatile VADs) and 8 nonfailing 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 were analyzed using Microarray Analysis Suite 5.0 (Affymetrix) and clustered by Expressionist software (Genedata). We found 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 >or=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 nonpulsatile 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 nonpulsatile VAD-supported hearts did not provide evidence for a pump mode-specific transcriptome pattern.
authors.affiliation: Herz- und Diabeteszentrum NRW, Klinik für Thorax- und Kardiovaskularchirurgie, Erich und Hanna Klessmann-Institut für Kardiovaskuläre Forschung und Entwicklung, Ruhr Universität Bochum, Bad Oeynhausen, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schwientek
authors.forename: Peter
authors.initials: P
authors.lastname: Ellinghaus
authors.forename: Sonja
authors.initials: S
authors.lastname: Steppan
authors.forename: Donatella
authors.initials: D
authors.lastname: D'Urso
authors.forename: Michael
authors.initials: M
authors.lastname: Seewald
authors.forename: Astrid
authors.initials: A
authors.lastname: Kassner
authors.forename: Ramona
authors.initials: R
authors.lastname: Cebulla
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schulte-Eistrup
authors.forename: Michiel
authors.initials: M
authors.lastname: Morshuis
authors.forename: Daniela
authors.initials: D
authors.lastname: Röfe
authors.forename: Aly
authors.initials: A
authors.lastname: El Banayosy
authors.forename: Reiner
authors.initials: R
authors.lastname: Körfer
authors.forename: Hendrik
authors.initials: H
authors.lastname: Milting
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011673:Pulsatile Flow