TY - JOUR A1 - Sommer, Katharina A1 - Jakob, Heike A1 - Badjlan, Farsin A1 - Henrich, Dirk A1 - Frank, Johannes A1 - Marzi, Ingo A1 - Sander, Anna Lena T1 - 11,12 and 14,15 epoxyeicosatrienoic acid rescue deteriorated wound healing in ischemia T2 - PLoS one N2 - Introduction: Epoxyeicosatrienoic acids (EETs) are able to enhance angiogenesis and regulate inflammation that is especially important in wound healing under ischemic conditions. Thus, we evaluated the effect of local EET application on ischemic wounds in mice. Methods: Ischemia was induced by cautherization of two of the three supplying vessels to the mouse ear. Wounding was performed on the ear three days later. Wounds were treated either with 11,12 or 14,15 EET and compared to untreated control and normal wounds. Epithelialization was measured every second day. VEGF, TNF-α, TGF-β, matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP), Ki67, and SDF-1α were evaluated immunohistochemically in wounds on day 3, 6, and 9. Results: Ischemia delayed wound closure (12.8 days ± 1.9 standard deviation (SD) for ischemia and 8.0 days ± 0.94 SD for control). 11,12 and14,15 EET application ameliorated deteriorated wound healing on ischemic ears (7.6 ± 1.3 SD for 11,12 EET and 9.2 ± 1.4 SD for 14,15 EET). Ischemia did not change VEGF, TNF-α, TGF-β, SDF-1α, TIMP, MMP7 or MMP9 level significantly compared to control. Local application of 11,12 as well as 14,15 EET induced a significant elevation of VEGF, TGF-β, and SDF-1α expression as well as proliferation during the whole phase of wound healing compared to control and ischemia alone. Conclusion: In summary, EET improve impaired wound healing caused by ischemia as they enhance neovascularization and alter inflammatory response in wounds. Thus elevating lipid mediator level as 11,12 and 14,15 EET in wounds might be a successful strategy for amelioration of deranged wound healing under ischemia. KW - Wound healing KW - Ears KW - Ischemia KW - Inflammation KW - Vasculogenesis KW - Angiogenesis KW - Cytokines KW - Metalloproteases Y1 - 2019 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/48609 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-486090 SN - 1932-6203 N1 - Copyright: © 2019 Sommer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. VL - 14 IS - (1): e0209158 SP - 1 EP - 15 PB - PLoS CY - Lawrence, Kan. ER -