Cardiac outflow tract malformations in chick embryos exposed to homocysteine
Cardiac outflow tract malformations in chick embryos exposed to homocysteine
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DOI：
10.1016/j.cardiores.2004.07.010
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发表时间：
2004-11-01
影响因子：
10.8
通讯作者：
Gittenberger-de Groot, AC
中科院分区：
文献类型：
--
作者：
Boot, MJ;Steegers-Theunissen, RPM;Gittenberger-de Groot, AC
目的：同型半胱氨酸浓度升高与心脏流出道缺陷有关。据推测，心脏神经嵴细胞是这些畸形的靶细胞。心脏神经嵴细胞从神经管迁移到主动脉肺隔和心脏流出道垫的凝聚间质中。本研究的目的是探讨同型半胱氨酸对心脏神经嵴细胞的影响与心脏畸形有关。方法：将同型半胱氨酸分别注入鸡胚神经管腔（30 μ mol/l）和循环系统（30 μ mol/l或300 μ mol/l）。lacz -逆转录病毒标记用于研究暴露于同型半胱氨酸后心脏神经嵴细胞的迁移途径。结果：心脏神经嵴细胞对对照组和同型半胱氨酸处理的胚胎的主动脉肺间隔都有贡献。然而，注射同型半胱氨酸-神经管的胚胎流出道细胞凋亡减少60%，心肌化减少25%。在83%的胚胎中观察到动脉下室间隔缺损。在同型半胱氨酸循环系统注射的胚胎中未观察到这些异常。结论：本研究表明，同型半胱氨酸可能通过影响心脏神经嵴细胞来干扰流出道细胞凋亡和心肌化。(C) 2004欧洲心脏病学会。Elsevier B.V.版权所有。
Objective: Increased homocysteine concentrations have been associated with cardiac outflow tract defects. It has been hypothesized that cardiac neural crest cells were the target cells in these malformations. Cardiac neural crest cells migrate from the neural tube and contribute to the condensed mesenchyme of the aorticopulmonary septum and outflow tract cushions of the heart. The aim of this study is to investigate the effects of homocysteine on cardiac neural crest cells in relation to heart malformations.Methods: Homocysteine was injected either into the neural tube lumen (30 mumol/l), or into the circulatory system (30 or 300 mumol/l) of chick embryos. LacZ-retroviral labeling was used to study cardiac neural crest cell migratory pathways after exposure to homocysteine.Results: Cardiac neural crest cells contributed to the aorticopulmonary septum of both control and homocysteine-treated embryos. However, the outflow tract of homocysteine-neural tube injected embryos displayed 60% less apoptosis and 25% reduced myocardialization. A subarterial ventricular septal defect was observed in 83% of the embryos. None of these abnormalities were observed in homcysteine-circulatory system injected embryos.Conclusion: This study demonstrates that homocysteine disturbs apoptosis and myocardialization of the outflow tract, probably by affecting the cardiac neural crest cells. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.