{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:52:17Z","timestamp":1791917537021,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Cell Communication and Signaling"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Endothelial\u2010derived reactive oxygen species (ROS), modulated by free iron levels, are key drivers of neutrophil extracellular traps (NETs) formation and contribute to cerebral ischemia\/reperfusion (CI\/R) injury. Targeting ROS and iron could possibly reduce NETs formation and mitigate stroke. NETs were predominantly initiated by hypoxia\/reoxygenation (H\/R) in endothelial cells (ECs), rather than in neutrophils. Silencing Fpn1 in ECs significantly reduced extracellular iron, suppressed ROS production, and inhibited NETs formation\u2014effects that were reversed by supplementation with iron or hemin. Additionally, both vitamin C (Vc) and deferoxamine (DFOM) suppressed blood coagulation on Fpn1\u2010silenced ECs under H\/R conditions. NETs formation on hypoxic ECs was further enhanced in the presence of co\u2010cultured red blood cells. In a mouse model of middle cerebral artery occlusion, combined treatment with Vc and DFOM synergistically reduced infarct size. Although Vc or DFOM alone reduced NETs formation, their combined use showed a weaker effect than DFOM alone, possibly because better blood flow increased neutrophil contact with the endothelium. In conclusion, endothelial ROS and iron play critical roles in regulating NETs formation during CI\/R injury. Combined treatment with Vc and DFOM offers a promising therapeutic strategy to reduce stroke\u2010induced damage by modulating ROS levels and NETs formation.<\/jats:p>","DOI":"10.1002\/ccs3.70050","type":"journal-article","created":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T04:55:13Z","timestamp":1759553713000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Iron enhances reactive oxygen species generation and initiates neutrophil extracellular traps formation on the endothelium to exacerbate stroke"],"prefix":"10.1002","volume":"19","author":[{"given":"Weijian","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zebin","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The 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