Blood flow suppresses vascular Notch signalling via dll4 and is required for angiogenesis in response to hypoxic signalling.
Blood flow suppresses vascular Notch signalling via dll4 and is required for angiogenesis in response to hypoxic signalling.
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DOI：
10.1093/cvr/cvt170
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发表时间：
2013-11-01
影响因子：
10.8
通讯作者：
Chico TJ
中科院分区：
文献类型：
--
作者：
Watson O;Novodvorsky P;Gray C;Rothman AM;Lawrie A;Crossman DC;Haase A;McMahon K;Gering M;Van Eeden FJ;Chico TJ
血流对血管生成的贡献还不完全清楚。我们研究了血流对斑马鱼胚胎血管系统中Notch信号传导的影响，以及血流是否通过组成性上调缺氧信号传导来调节斑马鱼的血管生成。发育中的斑马鱼（Danio rerio）胚胎通过扩散存活，在没有通过敲低心肌肌钙蛋白T2或化学心脏停止诱导的循环的情况下。在受精后48小时的老胚胎中，血流的缺乏通过上调Notch配体dll4增加了血管Notch信号传导。尽管如此，段间血管的模式不受血流缺乏的影响。因此，我们研究了具有组成性上调缺氧信号传导的纯合vhl突变斑马鱼。这些显示过度和异常的血管生成从受精后72小时，显着增加内皮细胞数量，血管直径和长度。血流的缺乏消除了这些影响，但正常的血管图案被保留下来。我们发现，血流通过下调dll4抑制血管Notch信号传导。我们还表明，血流是血管生成所需的缺氧信号，但不需要正常的血管图案。这些数据表明低氧驱动的血管生成与发育性血管生成的重要差异。
The contribution of blood flow to angiogenesis is incompletely understood. We examined the effect of blood flow on Notch signalling in the vasculature of zebrafish embryos, and whether blood flow regulates angiogenesis in zebrafish with constitutively up-regulated hypoxic signalling. Developing zebrafish (Danio rerio) embryos survive via diffusion in the absence of circulation induced by knockdown of cardiac troponin T2 or chemical cardiac cessation. The absence of blood flow increased vascular Notch signalling in 48 h post-fertilization old embryos via up-regulation of the Notch ligand dll4. Despite this, patterning of the intersegmental vessels is not affected by absent blood flow. We therefore examined homozygous vhl mutant zebrafish that have constitutively up-regulated hypoxic signalling. These display excessive and aberrant angiogenesis from 72 h post-fertilization, with significantly increased endothelial number, vessel diameter, and length. The absence of blood flow abolished these effects, though normal vessel patterning was preserved. We show that blood flow suppresses vascular Notch signalling via down-regulation of dll4. We have also shown that blood flow is required for angiogenesis in response to hypoxic signalling but is not required for normal vessel patterning. These data indicate important differences in hypoxia-driven vs. developmental angiogenesis.
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影响因子：
2.7
作者：
Blum, Yannick;Belting, Heinz-Georg;Affolter, Markus
通讯作者：
Affolter, Markus
影响因子：
20.3
作者：
Bridge, Gemma;Monteiro, Rui;Boshoff, Chris
通讯作者：
Boshoff, Chris
DOI：
10.1016/j.bbrc.2012.12.118
发表时间：
2013-02-08
影响因子：
3.1
作者：
Ma, Yimin;Ren, Yongxin;Han, Ethan Q.;Li, Huiwu;Chen, Di;Jacobs, Joshua J.;Gitelis, Steven;O'Keefe, Regis J.;Konttinen, Yrjo T.;Yin, Guoyong;Li, Tian-Fang
通讯作者：
Li, Tian-Fang
影响因子：
8.3
作者：
Madanecki P;Kapoor N;Bebok Z;Ochocka R;Collawn JF;Bartoszewski R
通讯作者：
Bartoszewski R
影响因子：
--
作者：
Gridley, Thomas
通讯作者：
Gridley, Thomas