ABSTRACT NUMBER: ESOC2026A1605 INTRA-PLAQUE NEUTROPHIL EXTRACELLULAR TRAPS IN CAROTID ARTERY STENOSIS: ASSOCIATION WITH VULNERABILITY AND STROKE

Abstract Background and aims Neutrophil extracellular traps (NETs) have been implicated in vascular inflammation and thromboinflammatory processes that contribute to atherosclerotic plaque vulnerability and athero-thrombosis. However, their role in human carotid plaques associated with ischemic stroke remains insufficiently characterized. Methods Carotid endarterectomy specimens from patients with symptomatic and asymptomatic carotid stenosis as well as peripheral venous blood samples taken prior to intervention and at a 90-day follow-up were analyzed. Blood-based NETs markers (cfDNA, DNase activity, H3cit) were determined. Immunohistochemical staining for established NET markers DNA-histone-1 complexes and myeloperoxidase (MPO) was performed and analyzed in carotid plaque samples. A semi-quantitative NETs score was established to investigate the association between NETs burden and clinical as well as histopathological features of plaque vulnerability. Results 48 patients (mean age: 69 years, 25% female) were included. Symptomatic carotid plaques (n= 22) exhibited markedly higher NETs burden compared to asymptomatic plaques (n=24): p=0.03. Moreover, the NETs score correlated with histopathological features of plaque vulnerability (rs=0.333, p=0.029). No differences were found in blood-based NETs markers between symptomatic and asymptomatic patients at baseline. At 90 days, DNase activity tended to be lower in blood samples of symptomatic patients with a significant delta to baseline (DNase activity 90d [pmol/min/ml]: symp= 16.56 vs. asymp=16.88, p=0.083, Delta DNase activity: symp= 1.47 vs asymp= -1.51, p=0.012). Conclusions Plaque-based burden of NETs is associated with vulnerability and stroke in carotid artery stenosis. The findings of this pilot study therefore underscore the potential role of NETs in stroke in carotid artery disease. Conflict of interest Ramona Schuppner: nothing to disclose, Ricarda D. Stauss: nothing to disclose, Claudia Schrimpf: nothing to disclose, Mathias Wilhelmi: nothing to disclose, Maria M. Gabriel: nothing to disclose, Lavinia Neubert´: nothing to disclose, Danny D. Jonigk: nothing to disclose, Karin Weissenborn: nothing to disclose, Nicole de Buhr: nothing to disclose, Gerrit M. Grosse: nothing to disclose