Cardiovascular Development and Disease Altered Hemodynamics in the Embryonic Heart Affects Outflow Valve Development
Cardiovascular Development and Disease Altered Hemodynamics in the Embryonic Heart Affects Outflow Valve Development
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通讯作者：
Vinal Menon;J. Eberth;R. Goodwin;J. Potts;Cheryl L. Maslen;Russell Norris
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作者：
Vinal Menon;J. Eberth;R. Goodwin;J. Potts;Cheryl L. Maslen;Russell Norris
心脏瓣膜的结构和功能主要是在发育早期决定的。因此，畸形心脏瓣膜是最常见的先天性心脏缺陷类型。一些成人瓣膜疾病可以追溯到瓣膜发育异常，因此必须完全了解心脏瓣膜发育的过程和调节。上皮间充质转化(EMT)在心脏瓣膜发育过程中起着重要作用。虽然血流动力学对瓣膜的发育至关重要，但它在调节EMT中的作用仍不清楚。在本研究中，通过收缩HH16-17(Hamilton and Hamburger(HH)阶段16-17)鸡胚胎的流出道(OFT)/心室交界处(OVJ)24小时来改变心内血流动力学，这种收缩使流出道沿流出道(OFT)的峰值和时间平均中心线速度增加，而体积流量和心率不变。计算流体力学被用来估计来自Amira重建的OFT垫上增加的空间平均壁切应力水平。在开放通道中，经常收缩导致OFT垫体积和侵袭间充质的数量显著减少。定量聚合酶链式反应分析显示，在有条带的心脏的OFT垫中，对瓣膜发育至关重要的一组具有代表性的基因的mRNA表达发生了变化。这项研究表明血流动力学在瓣膜发育中的重要性。
Cardiac valve structure and function are primarily determined during early development. Consequently, abnormally-formed heart valves are the most common type of congenital heart defects. Several adult valve diseases can be backtracked to abnormal valve development, making it imperative to completely understand the process and regulation of heart valve development. Epithelial-to-mesenchymal transition (EMT) plays an important role in the development of heart valves. Though hemodynamics is vital to valve development, its role in regulating EMT is still unknown. In this study, intracardiac hemodynamics were altered by constricting the outflow tract (OFT)/ventricle junction (OVJ) of HH16–17 (Hamilton and Hamburger (HH) Stage 16–17) chicken embryos, ex ovo for 24 h. The constriction created an increase in peak and time-averaged centerline velocity along the OFT without changes to volumetric flow or heart rate. Computational fluid dynamics was used to estimate the level of increased spatially-averaged wall shear stresses on the OFT cushion from AMIRA reconstructions. OFT constriction led to a significant decrease in OFT cushion volume and the number of invaded mesenchyme in OPEN ACCESS 109 the OFT cushion. qPCR analysis revealed altered mRNA expression of a representative panel of genes, vital to valve development, in the OFT cushions from banded hearts. This study indicates the importance of hemodynamics in valve development.