Cardiac neural crest orchestrates remodeling and functional maturation of mouse semilunar valves
Cardiac neural crest orchestrates remodeling and functional maturation of mouse semilunar valves
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DOI：
10.1172/jci44244
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发表时间：
2011-01-01
影响因子：
15.9
通讯作者：
Epstein, Jonathan A.
中科院分区：
文献类型：
--
作者：
Jain, Rajan;Engleka, Kurt A.;Epstein, Jonathan A.
主动脉瓣的先天性异常是常见的，并且与进行性瓣膜关闭不全和/或狭窄相关。此外，动脉瘤、缩窄、升主动脉和主动脉弓的夹层通常是使患者管理复杂化并增加发病率和死亡率的相关病症。这些相关的动脉病变通常归因于通过畸形瓣膜的湍流血流动力学流动，导致血管壁中的局灶性缺损。然而，许多手术和病理学研究已经确定了广泛的囊性中膜坏死和平滑肌细胞凋亡，在整个主动脉弓的影响患者在这里，我们提供了一个替代模型的实验证据，以解释主动脉血管和瓣膜疾病的关联使用小鼠与原发性和继发性心脏神经嵴缺陷，我们已经表明，神经嵴对流出内膜垫的贡献（半月瓣的前体）是妊娠晚期瓣膜重塑，间质细胞凋亡，神经嵴也被证明有助于升主动脉和主动脉弓壁的平滑肌层。因此，心脏神经嵴的缺陷可导致半月瓣功能异常和伴随的主动脉弓动脉异常。
Congenital anomalies of the aortic valve are common and are associated with progressive valvular insufficiency and/or stenosis In addition, aneurysm, coarctation, and dissection of the ascending aorta and aortic arch are often associated conditions that complicate patient management and increase morbidity and mortality These associated aortopathies are commonly attributed to turbulent hemodynamic flow through the malformed valve leading to focal defects in the vessel wall However, numerous surgical and pathological studies have identified widespread cystic medial necrosis and smooth muscle apoptosis throughout the aortic arch m affected patients Here, we provide experimental evidence for an alternative model to explain the association of aortic vessel and valvular disease Using mice with primary and secondary cardiac neural crest deficiencies, we have shown that neural crest contribution to the outflow endocardial cushions (the precursors of the semilunar valves) is required for late gestation valvular remodeling, mesenchymal apoptosis, and proper valve architecture Neural crest was also shown to contribute to the smooth muscle layer of the wall of the ascending aorta and aortic arch Hence, defects of cardiac neural crest can result m functionally abnormal semilunar valves and concomitant aortic arch artery abnormalities