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| Item Type: | Preprint |
|---|---|
| Title: | Pial collaterals develop through mosaic colonization of capillaries by arterial and microvascular endothelial cells |
| Creators Name: | Perovic, T., Hollfinger, I., Mayer, S., Lips, J., Dopatka, M., Harms, C. and Gerhardt, H. |
| Abstract: | Collaterals are unique blood vessels present in many healthy tissues that cross-connect distal-end arterioles of adjacent arterial trees, thus providing alternate routes of perfusion. Stroke patients with superior pial collateral flow respond better to treatments and present with an overall improved prognostic outcome. However, how pial collaterals develop in the embryo and how they reactivate upon stroke remains unclear. Here, using lineage tracing in combination with three-dimensional imaging, we demonstrate that mouse embryos employ a novel mechanism to build pial collaterals, distinct from their outward remodeling following stroke. Endothelial cells (ECs) of arterial and microvascular origin invade already existing pre-collateral vascular structures in a process which we termed mosaic colonization. Arterialization of these pre-collateral vascular segments happens concurrently with mosaic colonization. Despite having a smaller proliferative capacity, embryonic arterial cells represent the majority of cells that migrate to form nascent collaterals; embryonic microvascular cells, despite their higher proliferative potential, form only about a quarter of collateral endothelial cells. Moreover, postnatal collateral growth relies much more on self-replenishment of arterial cells than on microvascular contribution. Following ischemic injury, pial collateral outward remodeling relies on local cell proliferation rather than recruitment of non-arterial cells. Together, these findings establish distinct cellular mechanisms underlying pial collateral development and ischemic remodeling, raising the prospect for future research to identify novel, collateral-specific therapeutic strategies for ischemic stroke. |
| Keywords: | Pial Vasculature, Endothelium, Collateral Development, Angiogenesis, Vollateral Remodeling, Animals, Mice |
| Source: | bioRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2023.10.09.561542v3 |
| Date: | 7 February 2024 |
| Official Publication: | https://doi.org/10.1101/2023.10.09.561542 |
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