Summary
Neutrophil extracellular traps (NETs) are networks of DNA, histones, and proteolytic
enzymes produced by activated neutrophils through different mechanisms. NET formation
is promoted by activated platelets and can in turn activate platelets, thus favoring
thrombotic processes. NETs have been detected in venous and arterial thrombosis, but
data in stroke are scarce. The aim of this study was to evaluate NETs in the plasma
of patients with acute ischemic stroke and their potential association with baseline
clinical characteristics, stroke severity, and one-year clinical outcomes. The study
included 243 patients with acute ischemic stroke. Clinical and demographic data and
scores of stroke severity (NIHSS and mRs) at onset and discharge were recorded. Markers
of NETs (cell-free DNA, nucleosomes, and citrullinated histone 3 (citH3)), were determined
in plasma. Patients were followed-up for 12 months after the ischemic event. NETs
were significantly elevated in the plasma of patients with acute ischemic stroke when
compared to healthy subjects. NETs were increased in patients who were over 65 years
of age and in those with a history of atrial fibrillation (AF), cardioembolic stroke,
high glucose levels, and severe stroke scores at admission and discharge. In multivariate
analysis, elevated levels of citH3, the most specific marker of NETs, at onset were
independently associated with AF and all-cause mortality at oneyear follow-up. NETs
play a role in the pathophysiology of stroke and are associated with severity and
mortality. In conclusion, citH3 may constitute a useful prognostic marker and therapeutic
target in patients with acute stroke.
Keywords
Stroke - extracellular traps - atrial fibrillation - glucose - immunity