Vascular remodeling of the mouse yolk sac requires hemodynamic force
Vascular remodeling of the mouse yolk sac requires hemodynamic force
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DOI：
10.1242/dev.02883
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发表时间：
2007-09-15
期刊：
影响因子：
4.6
通讯作者：
Dickinson, Mary E.
中科院分区：
文献类型：
--
作者：
Lucitti, Jennifer L.;Jones, Elizabeth A. V.;Dickinson, Mary E.
胚胎心脏和血管是动态的，在功能性的同时形成和重塑。关于心血管系统发育的遗传机制已经了解了很多，但我们才刚刚开始了解心脏和血管结构的变化如何受到血流动力学力（如剪切力）的影响。最近的研究表明，当心脏功能降低或缺失时，小鼠卵黄囊中的血管重塑受到继发性影响。这些发现表明，血管重塑需要适当的循环，但尚未确定循环的作用是提供机械线索，输送氧气还是循环信号分子。在这里，我们使用时间推移共聚焦显微镜，以确定在发展中的小鼠卵黄囊的血管重塑中的流体衍生的力量的作用。新的方法被用来表征正常胚胎和收缩性受损的胚胎（Mlc 2a（-/-））的流动。我们在这些胚胎中发现了异常的血浆和成红细胞循环，这使我们假设成红细胞进入循环是触发血管重塑的关键事件。我们通过隔离血岛中的成红细胞来测试这一点，从而降低血细胞比容和降低剪切应力，并发现血管重塑和eNOS（Nos 3）的表达取决于成红细胞流量。此外，我们通过恢复血液粘度来挽救低血细胞比容胚胎中的重塑缺陷和eNOS表达。这些数据表明，血液动力学的力量是必要的，足以诱导哺乳动物卵黄囊血管重塑。
The embryonic heart and vessels are dynamic and form and remodel while functional. Much has been learned about the genetic mechanisms underlying the development of the cardiovascular system, but we are just beginning to understand how changes in heart and vessel structure are influenced by hemodynamic forces such as shear stress. Recent work has shown that vessel remodeling in the mouse yolk sac is secondarily effected when cardiac function is reduced or absent. These findings indicate that proper circulation is required for vessel remodeling, but have not defined whether the role of circulation is to provide mechanical cues, to deliver oxygen or to circulate signaling molecules. Here, we used time-lapse confocal microscopy to determine the role of fluid-derived forces in vessel remodeling in the developing murine yolk sac. Novel methods were used to characterize flows in normal embryos and in embryos with impaired contractility (Mlc2a(-/-)). We found abnormal plasma and erythroblast circulation in these embryos, which led us to hypothesize that the entry of erythroblasts into circulation is a key event in triggering vessel remodeling. We tested this by sequestering erythroblasts in the blood islands, thereby lowering the hematocrit and reducing shear stress, and found that vessel remodeling and the expression of eNOS (Nos3) depends on erythroblast flow. Further, we rescued remodeling defects and eNOS expression in low-hematocrit embryos by restoring the viscosity of the blood. These data show that hemodynamic force is necessary and sufficient to induce vessel remodeling in the mammalian yolk sac.