Impaired Development of Left Anterior Heart Field by Ectopic Retinoic Acid Causes Transposition of the Great Arteries
Impaired Development of Left Anterior Heart Field by Ectopic Retinoic Acid Causes Transposition of the Great Arteries
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DOI：
10.1161/jaha.115.001889
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发表时间：
2015-04
期刊：
影响因子：
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通讯作者：
Mayu Narematsu;Tatsuya Kamimura;T. Yamagishi;M. Fukui;Y. Nakajima
中科院分区：
文献类型：
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作者：
Mayu Narematsu;Tatsuya Kamimura;T. Yamagishi;M. Fukui;Y. Nakajima
背景 大动脉转位是出生时最常诊断的圆锥干心脏缺陷之一，但其病因很大程度上未知。位于前咽弓的前心区 (AHF) 有助于圆锥干发育，在此期间，源自左右 AHF 的心脏祖细胞迁移形成不同的圆锥干区域。本研究的目的是确定导致大动脉转位形态的异常 AHF 发育。方法和结果 我们将视黄酸浸泡的珠子放置在 12 至 14 期鸡胚 AHF 的左侧、右侧或两侧，并在 34 期检查圆锥干心脏缺陷。在 12 期将视黄酸浸泡的珠子放置在左侧 AHF 的胚胎中，大动脉转位的发生率较高。荧光染料示踪显示 AHF 暴露于视黄酸 酸未能促进圆锥干的发育。在暴露于视黄酸的 AHF 中，FGF8 和 Isl1 表达下调，并且在补充有视黄酸的培养基中培养的 AHF 中，心肌细胞的分化和扩张受到抑制。结论 早期环心期左侧AHF，相当于人类胚胎卡内基10～11期（受精后28～29天），是引起大动脉转位形态的障碍区域。
Background Transposition of the great arteries is one of the most commonly diagnosed conotruncal heart defects at birth, but its etiology is largely unknown. The anterior heart field (AHF) that resides in the anterior pharyngeal arches contributes to conotruncal development, during which heart progenitors that originated from the left and right AHF migrate to form distinct conotruncal regions. The aim of this study is to identify abnormal AHF development that causes the morphology of transposition of the great arteries. Methods and Results We placed a retinoic acid–soaked bead on the left or the right or on both sides of the AHF of stage 12 to 14 chick embryos and examined the conotruncal heart defect at stage 34. Transposition of the great arteries was diagnosed at high incidence in embryos for which a retinoic acid–soaked bead had been placed in the left AHF at stage 12. Fluorescent dye tracing showed that AHF exposed to retinoic acid failed to contribute to conotruncus development. FGF8 and Isl1 expression were downregulated in retinoic acid–exposed AHF, and differentiation and expansion of cardiomyocytes were suppressed in cultured AHF in medium supplemented with retinoic acid. Conclusions The left AHF at the early looped heart stage, corresponding to Carnegie stages 10 to 11 (28 to 29 days after fertilization) in human embryos, is the region of the impediment that causes the morphology of transposition of the great arteries.