Preprint Article Version 1 This version is not peer-reviewed

Endothelial Dysfunction and Impaired Wound Healing Following Radiation Combined Skin Wound Injury

Version 1 : Received: 30 October 2024 / Approved: 31 October 2024 / Online: 2 November 2024 (03:50:52 CET)

How to cite: Wang, L.; Lin, B.; Zhai, M.; Hull, L.; Cui, W.; Xiao, M. Endothelial Dysfunction and Impaired Wound Healing Following Radiation Combined Skin Wound Injury. Preprints 2024, 2024102603. https://doi.org/10.20944/preprints202410.2603.v1 Wang, L.; Lin, B.; Zhai, M.; Hull, L.; Cui, W.; Xiao, M. Endothelial Dysfunction and Impaired Wound Healing Following Radiation Combined Skin Wound Injury. Preprints 2024, 2024102603. https://doi.org/10.20944/preprints202410.2603.v1

Abstract

Currently, there are no U.S. Food and Drug Administration (FDA)-approved medical countermeasures (MCMs) for radiation combined injury (RCI), partially due to limited understanding of its mechanisms. Our previous research suggests that endothelial dysfunction may contribute to a poor prognosis of RCI. In this study, we demonstrated an increased risk of mortality, body weight loss and delated skin wound healing in RCI mice compared to mice with skin wound alone or radiation injury (RI) 30 days post-insult. Furthermore, we evaluated biomarkers of endothelial dysfunction, inflammation, and impaired wound healing in mouse at early time points after RCI. Mice were exposed to 9.0 Gy total body irradiation (TBI) followed by skin wound. Samples were collected on days 3, 7, and 14 post-TBI. Endothelial dysfunction markers were measured by ELISA, and skin wound healing was assessed histologically. Our results show that endothelial damage and inflammation are more severe and persistent in RCI compared to wound-alone. Additionally, RCI impairs granulation tissue formation, reduces myofibroblast presence, and delays collagen deposition, correlating with more severe endothelial damage. TGF signaling may plays a key role in this impaired healing. These findings suggest that targeting endothelial dysfunction and TGF-β pathways may provide potential therapeutic strategies for improving delayed wound healing in RCI, which could subsequently influence outcomes such as survival after RCI.

Keywords

radiation combined skin wound injury; impaired wound healing; endothelial dysfunction; systemic and local proinflammatory response; TGFβ expression; granulation tissue formation; myofibroblast; collagen deposition

Subject

Medicine and Pharmacology, Cardiac and Cardiovascular Systems

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