Document Type
Article
Publication Date
8-2-2023
Original Citation
Dastagir K,
Gamrekelashvili J,
Dastagir N,
Limbourg A,
Kijas D,
Kapanadze T,
Vogt P,
Limbourg F.
A new fasciocutaneous flap model identifies a critical role for endothelial Notch signaling in wound healing and flap survival. Sci Rep. 2023;13(1):12542.
Keywords
JMG, Mice, Animals, Endothelial Cells, Neovascularization, Physiologic, Calcium-Binding Proteins, Wound Healing, Inflammation
JAX Source
Sci Rep. 2023;13(1):12542.
ISSN
2045-2322
PMID
37532879
DOI
https://doi.org/10.1038/s41598-023-39722-1
Grant
Open Access funding enabled and organized by Projekt DEAL
Abstract
Flap surgery is a common treatment for severe wounds and a major determinant of surgical outcome. Flap survival and healing depends on adaptation of the local flap vasculature. Using a novel and defined model of fasciocutaneous flap surgery, we demonstrate that the Notch ligand Delta-like 1 (Dll1), expressed in vascular endothelial cells, regulates flap arteriogenesis, inflammation and flap survival. Utilizing the stereotyped anatomy of dorsal skin arteries, ligation of the major vascular pedicle induced strong collateral vessel development by end-to-end anastomosis in wildtype mice, which supported flap perfusion recovery over time. In mice with heterozygous deletion of Dll1, collateral vessel formation was strongly impaired, resulting in aberrant vascularization and subsequent necrosis of the tissue. Furthermore, Dll1 deficient mice showed severe inflammation in the flap dominated by monocytes and macrophages. This process is controlled by endothelial Dll1 in vivo, since the results were recapitulated in mice with endothelial-specific deletion of Dll1. Thus, our model provides a platform to study vascular adaptation to flap surgery and molecular and cellular regulators influencing flap healing and survival.
Comments
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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.