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However, the specific mechanism underlying vascular injury caused by NETs remains unclear. Immunofluorescence, ELISA, and flow cytometry were used in this study to detect the expression of NETs and DNase in the tissue and peripheral blood samples of patients with IBD. DSS mouse model was used to detect colon injury and vascular permeability. We found that NETs and DNase levels increased in the colon of patients with IBD. We found an increase in the activity of NET\u2010related MPO released by DNase. DNase released NET\u2010related proteins and damaged vascular endothelial cells in\u00a0vitro. In DSS mouse model, the synchronous increase of DNase and NETs in the colon leads to an increase in vascular injury markers (CD44, sTM). DNase aggravated colon injury and increased vascular permeability in\u00a0vivo, which was inhibited by gentamicin sulfate (GS). GS does not reduce the expression of DNase, but rather reduces the release of NET\u2010related proteins to protect vascular endothelium by inhibiting DNase activity. MPO and histones synergistically damaged the vascular endothelium, and vascular injury can be improved by their active inhibitors. We further found that H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    is an important substrate for MPO induced vascular damage. In conclusion, in IBD, DNase, and NET levels increased synchronously in the lesion area and released NET\u2010related proteins to damage the vascular endothelium. Therefore, targeting DNase may be beneficial for the treatment of IBD.\n                  <\/jats:p>","DOI":"10.1096\/fj.202301780r","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T09:26:10Z","timestamp":1703669170000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["<scp>DNase<\/scp>\n                    aggravates intestinal microvascular injury in\n                    <scp>IBD<\/scp>\n                    patients by releasing\n                    <scp>NET<\/scp>\n                    \u2010related proteins"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3999-7242","authenticated-orcid":false,"given":"Yiming","family":"Shao","sequence":"first","affiliation":[{"name":"Department of Burns and Plastic Surgery Affiliated Hospital of Jining Medical University  Jining China"},{"name":"Research Center for Neutrophil Engineering Technology 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