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. 2022 Jun 14;54(6):711–719. doi: 10.1038/s12276-022-00785-1

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — Venous endothelial cells migrate against blood flow and differentiate into tip and arterial endothelial cells. Cells in hypoxic areas release angiogenic factors, including VEGF-A, to initiate angiogenesis. This initiates venous endothelium migration into the vascular front via reverse migration. Venous endothelium-derived tip cells continue reverse migration and differentiate into arterial endothelial cells. Venous endothelial cells act as a primary source of ECs for angiogenic expansion through reverse migration.