Measuring hemodynamic changes during mammalian development
Measuring hemodynamic changes during mammalian development
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DOI：
10.1152/ajpheart.00081.2004
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发表时间：
2004-10-01
影响因子：
4.8
通讯作者：
Dickinson, ME
中科院分区：
文献类型：
--
作者：
Jones, EAV;Baron, MH;Dickinson, ME
许多先天性心血管疾病的发病机制涉及胚胎血管系统内的异常流动，其由心脏畸形或血管系统本身的缺陷引起。在小鼠中进行的广泛的遗传和基因组分析已经导致鉴定出在胚胎发育期间导致心血管缺陷的一系列突变。这些突变中的许多在脉管系统内引起被认为是由于流体动力学改变而引起的继发性效应。据推测，心脏缺陷会干扰或减少血流，从而导致正常血管发育所需的机械信号中断。不幸的是，准确理解如何流中断导致继发性血管缺陷已受到现有分析工具的不足。在这里，我们使用了一种快速的线扫描技术在小鼠胚胎早期器官形成过程中的血流动力学的定量分析，我们提出了一个模型系统，用于研究哺乳动物心血管系统的形成和重塑过程中的细胞反应。即使在新形成的血管中，只要心脏开始跳动，就可以测量流速曲线。这些研究建立了血管系统内血流模式与心脏发育阶段之间的联系，并能够分析发育过程中机械力的影响。
The pathogenesis of many congenital cardiovascular diseases involves abnormal flow within the embryonic vasculature that results either from malformations of the heart or defects in the vasculature itself. Extensive genetic and genomic analysis in mice has led to the identification of an array of mutations that result in cardiovascular defects during embryogenesis. Many of these mutations cause secondary effects within the vasculature that are thought to arise because of altered fluid dynamics. Presumably, cardiac defects disturb or reduce flow and thereby lead to the disruption of the mechanical signals necessary for proper vascular development. Unfortunately, a precise understanding of how flow disruptions lead to secondary vasculature defects has been hampered by the inadequacy of existing analytical tools. Here, we used a fast line-scanning technique for the quantitative analysis of hemodynamics during early organogenesis in mouse embryos, and we present a model system for studying cellular responses during the formation and remodeling of the mammalian cardiovascular system. Flow velocity profiles can be measured as soon as a heart begins to beat even in newly formed vessels. These studies establish a link between the pattern of blood flow within the vasculature and the stage of heart development and also enable analysis of the influence of mechanical forces during development.