Iron enhances reactive oxygen species generation and initiates neutrophil extracellular traps formation on the endothelium to exacerbate stroke.

ABSTRACT: Endothelial-derived 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-effects that were reversed by supplementation with iron or hemin. Additionally, both vitamin C (Vc) and deferoxamine (DFOM) suppressed blood coagulation on Fpn1-silenced ECs under H/R conditions. NETs formation on hypoxic ECs was further enhanced in the presence of

SUBMITTER: Fan W 

PROVIDER: S-EPMC12494541 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature