Mechanism responsible for D-transposition of the great arteries: is this part of the spectrum of right isomerism?
Mechanism responsible for D-transposition of the great arteries: is this part of the spectrum of right isomerism?
复制标题
负责大动脉 D 型转位的机制：这是右异构谱的一部分吗？
DOI：
10.1111/cga.12176
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发表时间：
2016
影响因子：
1.3
通讯作者：
Nakajima Y
中科院分区：
文献类型：
--
作者：
Kato Masahiro;Narematsu Mayu;Nakajima Yuji;Nakajima Y
大动脉转位（TGA）是出生时最常见的圆锥状心脏缺陷之一，其特征是心室动脉连接不一致与房室连接不一致。TGA的形态学病因是心脏流出道（OFT， concon干）的反转或停止旋转，由此主动脉向右腹侧转位至肺动脉干。OFT的旋转缺陷被认为是由于肺下圆锥发育不全，其起源于位于第一和第二咽弓中胚层核心的左前心野（AHF）。AHF，尤其是左侧的AHF，在早期环状心脏阶段（对应于人类胚胎的卡内基阶段10-11）是导致TGA形态障碍的区域之一。在人类或实验产生的右同分异构体中，包括D - TGA在内的大动脉错位经常与之相关。涉及左右（L-R）不对称的基因突变，如asNODAL， actriib下游targetFOXH1，已在右同分异构体患者以及分离的TGA中发现。Nodal‐Foxh1的下游通路不仅在侧板中胚层的L-R决定中起关键作用，而且在AHF的心肌规范和分化中起关键作用，这表明TGA是异位的一种表型，也是AHF的主要发育缺陷。
D‐transposition of the great arteries (TGA) is one of the most common conotruncal heart defects at birth and is characterized by a discordant ventriculoarterial connection with a concordant atrioventricular connection. The morphological etiology of TGA is an inverted or arrested rotation of the heart outflow tract (OFT, conotruncus), by which the aorta is transposed in the right ventral direction to the pulmonary trunk. The rotational defect of the OFT is thought to be attributed to hypoplasia of the subpulmonic conus, which originates from the left anterior heart field (AHF) residing in the mesodermal core of the first and second pharyngeal arches. AHF, especially on the left, at the early looped heart stage (corresponding to Carnegie stage 10–11 in the human embryo) is one of the regions responsible for the impediment that causes TGA morphology. In human or experimentally produced right isomerism, malposition of the great arteries including D‐TGA is frequently associated. Mutations in genes involving left–right (L–R) asymmetry, such asNODAL,ACTRIIBand downstream targetFOXH1, have been found in patients with right isomerism as well as in isolated TGA. The downstream pathways of Nodal‐Foxh1 play a critical role not only in L–R determination in the lateral plate mesoderm but also in myocardial specification and differentiation in the AHF, suggesting that TGA is a phenotype in heterotaxia as well as the primary developmental defect of the AHF.