Association of Neutrophil Extracellular Traps with Plaque Instability in Patient with Carotid Artery Stenosis

Vulnerable carotid plaques are related to cerebral thromboembolic and ischemic events. Neutrophil extracellular traps (NETs) can induce endothelial dysfunction and induce inflammation and coagulation. The aim of the present study was to investigate NETs in patients with carotid artery plaques.Carotid plaques were collected by carotid endarterectomy (CEA) from 26 symptomatic and 8 asymptomatic patients between August 2017 and January 2021. The specimens were stained with hematoxylin-eosin and Elastica-van Gieson. Immunohistochemistry was performed staining by CD31 for identifying endothelial cells. NETs were detected by digoxigenin-labeled antihistone H3 (HH3) (citrulline R2+R8+R17). The relationships between the presence of NETs and patient profile and histopathological findings were assessed.HH3-positive cells were detected in 17 (asymptomatic = 2 symptomatic = 15) of 34 carotid plaques (median = 9.7/mm). The number of NETs was correlated with the number of diffusion-weighted imaging high-intensity lesions [P = 0.01], plaque rupture [P = 0.001], intraplaque hemorrhage [P = 0.02], intra luminal thrombus [P = 0.001], and thin fibrous cap [P = 0.001].The presence of NETs was associated with the instability of carotid plaques, intraluminal thrombus, which may lead to subsequent cerebral infarction. Clarifying the roles of NETs in carotid plaques may improve the treatment of carotid artery disease.