Wilson K S, Baily J, Tucker C S, Matrone G, Vass S, Moran C, Chapman K E, Mullins J J, Kenyon C, Hadoke P W F, Denvir M A
The British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK.
The British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK.
Mol Cell Endocrinol. 2015 Oct 15;414:120-31. doi: 10.1016/j.mce.2015.07.025. Epub 2015 Jul 26.
Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed.
Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 μm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/μm vs control 2.18 ± 0.13 cells/μm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 μg/mg vs controls 0.63 ± 0.06 μg/mg, p = 0.0007), had increased vmhc and gr mRNA levels.
Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart.
糖皮质激素（GC）在生命早期的短暂扰动与成年后心血管疾病风险相关。在此，评估了生命早期GC调控对成年心脏结构、功能和基因表达的影响。
斑马鱼胚胎在受精后的前120小时（hpf）用 dexamethasone（地塞米松，Dex）孵育或注射靶向糖皮质激素受体（GR）的吗啉代敲低剂（GR Mo）；存活的胚胎（>90%）在正常条件下饲养至成年。对胚胎期（120 hpf）和成年期（受精后120天，dpf）的心脏进行心脏功能、心脏组织学和心脏基因评估。与对照组相比，GR Mo胚胎（120 hpf）心脏较小，心肌细胞较少，横纹模式不成熟，心脏功能降低，vmhc和igf mRNA水平降低。与对照组相比，GR Mo成年心脏较小，小梁网络模式减少，vmhc表达降低，超声心动图多普勒血流改变。Dex胚胎在120 hpf时心脏较大（Dex 107.2±3.1 vs.对照组90.2±1.1μm，p<0.001），小梁网络更成熟，心肌细胞更大（1.62±0.13个细胞/μm vs对照组2.18±0.13个细胞/μm，p<0.05），心脏性能增强。成年心脏更大（1.02±0.07μg/mg vs对照组0.63±0.06μg/mg，p = 0.0007），vmhc和gr mRNA水平升高。
胚胎发育期间GR活性的扰动导致心脏的短期和长期改变。
