title: Transcriptome analysis of the response to chronic constant hypoxia in zebrafish hearts.
abstract: Insufficient blood supply during acute infarction and chronic ischemia leads to tissue hypoxia which can significantly alter gene expression patterns in the heart. In contrast to most mammals, some teleost fishes are able to adapt to extremely low oxygen levels. We describe here that chronic constant hypoxia (CCH) leads to a smaller ventricular outflow tract, reduced lacunae within the central ventricular cavity and around the trabeculae and an increase in the number of cardiac myocyte nuclei per area in the hearts of two teleost species, zebrafish (Danio rerio) and cichlids (Haplochromis piceatus). In order to identify the molecular basis for the adaptations to CCH, we profiled the gene expression changes in the hearts of adult zebrafish. We have analyzed over 15,000 different transcripts and found 376 differentially regulated genes, of which 260 genes showed increased and 116 genes decreased expression levels. Two notch receptors (notch-2 and notch-3) as well as regulatory genes linked to cell proliferation were transcriptionally upregulated in hypoxic hearts. We observed a simultaneous increase in expression of IGF-2 and IGFbp1 and upregulation of several genes important for the protection against reactive oxygen species (ROS). We have identified here many novel genes involved in the response to CCH in the heart, which may have potential clinical implications in the future.
authors.affiliation: Department of Integrative Zoology, Institute of Biology, University of Leiden, Wassenaarseweg 64, 2333 AL, Leiden, The Netherlands.
authors.forename: Ines J
authors.initials: IJ
authors.lastname: Marques
authors.forename: Jelani T D
authors.initials: JT
authors.lastname: Leito
authors.forename: Herman P
authors.initials: HP
authors.lastname: Spaink
authors.forename: Janwillem
authors.initials: J
authors.lastname: Testerink
authors.forename: Richard T
authors.initials: RT
authors.lastname: Jaspers
authors.forename: Frans
authors.initials: F
authors.lastname: Witte
authors.forename: Sjoerd
authors.initials: S
authors.lastname: van den Berg
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Bagowski
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002908:Chronic Disease; D023681:Cichlids / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015203:Reproducibility of Results; D013997:Time Factors; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*