New coronary vessels are added to the heart around birth to support postnatal cardiac growth. Here we show that, in late fetal development, the embryonic coronary plexus at the inner myocardium of the ventricles expresses the angiogenic signalling factors VEGFR3 and DLL4 and generates new coronary vessels in neonates. Contrary to a previous model in which the formation of new coronary vessels in neonates from ventricular endocardial cells was proposed, we find that late fetal and neonatal ventricular endocardial cells lack angiogenic potential and do not contribute to new coronary vessels. Instead, we show using lineage-tracing as well as gain- and loss-of-function experiments that the pre-existing embryonic coronary plexus at the inner myocardium undergoes angiogenic expansion through the DLL4–NOTCH1 signalling pathway to vascularize the expanding myocardium. We also show that the pre-existing coronary plexus revascularizes the regenerating neonatal heart through a similar mechanism. These findings provide a different model of neonatal coronary angiogenesis and regeneration, potentially informing cardiovascular medicine.

新的冠状血管在出生时被添加到心脏中，以支持产后心脏的生长。在这里，我们发现，在胎儿发育后期，心室内部心肌的胚胎冠状丛表达血管生成信号因子 VEGFR3 和 DLL4，并在新生儿中产生新的冠状血管。与之前提出的新生儿心室心内膜细胞形成新冠状血管的模型相反，我们发现晚期胎儿和新生儿心室心内膜细胞缺乏血管生成潜力，并且不会促进新冠状血管的形成。相反，我们通过谱系追踪以及功能获得和功能丧失实验表明，心肌内部预先存在的胚胎冠状丛通过 DLL4-NOTCH1 信号通路进行血管生成扩张，从而使扩张的心肌血管化。我们还表明，预先存在的冠状丛通过类似的机制使再生的新生儿心脏血运重建。这些发现提供了新生儿冠状动脉血管生成和再生的不同模型，可能为心血管医学提供信息。