While common in the general population, the developmental origins of “normal” anatomic variants of the aortic arch remain unknown. Aortic arch development begins with the establishment of the second heart field (SHF) that contributes to the pharyngeal arch arteries (PAAs). The PAAs remodel during subsequent development to form the mature aortic arch and arch vessels. Retinoic acid signaling involving the biologically active metabolite of vitamin A, plays a key role in multiple steps of this process. Recent work from our laboratory indicates that the E3 ubiquitin ligase Hectd1 is required for full activation of retinoic acid signaling during cardiac development. Furthermore, our study suggested that mild alterations in retinoic acid signaling combined with reduced gene dosage of Hectd1, results in a benign aortic arch variant where the transverse aortic arch is shortened between the brachiocephalic and left common carotid arteries. These abnormalities are preceded by hypoplasia of the fourth PAA. To further explore this interaction, we investigate whether reduced maternal dietary vitamin A intake can similarly influence aortic arch development. Our findings indicate that the incidence of hypoplastic fourth PAAs, as well as the incidence of shortened transverse arch are increased with reduced maternal vitamin A intake during pregnancy. These studies provide new insights as to the developmental origins of these benign aortic arch variants.

中文翻译：

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降低孕妇维生素A的状况会增加正常主动脉弓变异的发生率。

虽然在普通人群中很常见，但主动脉弓的“正常”解剖变异的发育起源仍然未知。主动脉弓的发展始于第二心脏场（SHF）的建立，该第二心脏场有助于咽弓动脉（PAA）。PAA在随后的发育过程中会重塑，形成成熟的主动脉弓和弓形血管。维甲酸信号涉及维生素A的生物活性代谢物，在该过程的多个步骤中起关键作用。我们实验室的最新工作表明，在心脏发育过程中，视黄酸信号的完全激活需要E3泛素连接酶Hectd1。此外，我们的研究表明，视黄酸信号的轻度改变与降低的Hectd1基因剂量相结合导致良性主动脉弓变体，其中横贯性主动脉弓在头臂和左颈总动脉之间缩短。在这些异常之前是第四PAA的发育不全。为了进一步探讨这种相互作用，我们研究了减少母体饮食中维生素A摄入量是否可以同样影响主动脉弓的发育。我们的发现表明，孕期孕妇维生素A摄入量减少会增加发育不良的第四PAA的发生率以及横弓缩短的发生率。这些研究为这些良性主动脉弓变体的起源提供了新的见识。