Perinatal angiogenesis from pre-existing coronary vessels via DLL4–NOTCH1 signalling

Lu, Pengfei and Wang, Yidong and Liu, Yang and Wang, Yifeng and Wu, Bingruo and Zheng, Deyou and Harvey, Richard P. and Zhou, Bin (2021) Perinatal angiogenesis from pre-existing coronary vessels via DLL4–NOTCH1 signalling. Nature Cell Biology, 23 (9). pp.967-977. ISSN 1465-7392

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Link to published document: http://doi.org/10.1038/s41556-021-00747-1

Abstract

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.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 10 Dec 2021 04:02
Last Modified: 10 Dec 2021 04:02
URI: http://eprints.victorchang.edu.au/id/eprint/1177

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