Marques Ines J, Leito Jelani T D, Spaink Herman P, Testerink Janwillem, Jaspers Richard T, Witte Frans, van den Berg Sjoerd, Bagowski Christoph P
Department of Integrative Zoology, Institute of Biology, University of Leiden, Wassenaarseweg 64, 2333 AL, Leiden, The Netherlands.
J Comp Physiol B. 2008 Jan;178(1):77-92. doi: 10.1007/s00360-007-0201-4. Epub 2007 Sep 8.
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.
急性梗死和慢性缺血期间的血液供应不足会导致组织缺氧，进而显著改变心脏中的基因表达模式。与大多数哺乳动物不同，一些硬骨鱼类能够适应极低的氧气水平。我们在此描述，慢性持续性缺氧（CCH）会导致斑马鱼（Danio rerio）和丽鱼科鱼（Haplochromis piceatus）这两种硬骨鱼类心脏的心室流出道变小、中央心室腔和小梁周围的腔隙减少以及单位面积心肌细胞核数量增加。为了确定适应CCH的分子基础，我们分析了成年斑马鱼心脏中的基因表达变化。我们分析了超过15000种不同的转录本，发现了376个差异调节基因，其中260个基因表达水平升高，116个基因表达水平降低。缺氧心脏中两个Notch受体（Notch-2和Notch-3）以及与细胞增殖相关的调节基因在转录水平上上调。我们观察到IGF-2和IGFbp1的表达同时增加，以及几个对抵御活性氧（ROS）重要的基因上调。我们在此鉴定出许多参与心脏对CCH反应的新基因，这些基因未来可能具有潜在的临床意义。
