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NETosis is associated with the severity of aortic stenosis: Links with inflammation.

Abstract：

BACKGROUND:An involvement of neutrophil extracellular traps (NETs) in the aortic stenosis (AS) pathogenesis is unknown. METHODS:We enrolled 50 patients, median age 66.5 years with isolated severe AS, after aortic valve replacement and 20 healthy sex/age-matched controls. Autopsy-derived aortic valves from 5 healthy donors served as controls. Valvular expression of citrullinated histone H3 (citH3), myeloperoxidase (MPO), and neutrophil elastase (NE) and macrophages (CD68) were evaluated by immunostaining. Plasma citH3 and interleukin 6 (IL-6) were also determined. RESULTS:All stenotic and healthy valves expressed citH3 in the leaflets' endothelial and sub-endothelial layers at the aortic side. Amount of valvular citH3-positive cells was higher in AS patients compared with controls (53.5 [33-62]% vs. 5.7 [4.1-9.0]%, p < 0.0001) and correlated with aortic valve area (AVA; r = -0.69, p < 0.0001) and mean transvalvular gradient (r = 0.6, p < 0.0001). Double-staining revealed that in AS valves 27.2 ± 9.8% of cells were citH3/MPO- and 25.3 ± 8.9% citH3/NE-positive. Within stenotic valves, 6.4 ± 2.5% of cells showed citH3/CD68 double-positivity and were identified as macrophages. AS patients compared to controls had 83% higher plasma citH3 (p < 0.0001). In AS, plasma citH3 correlated with IL-6 (r = 0.39, p = 0.0054) levels and AVA (r = -0.45, p = 0.0009). CONCLUSIONS:The presence of NETs in stenotic valves and association with AS severity suggest novel mechanisms involved in the disease progression.

journal_name

Int J Cardiol

journal_title

International journal of cardiology

authors

Kopytek M,Kolasa-Trela R,Ząbczyk M,Undas A,Natorska J

doi

10.1016/j.ijcard.2019.03.047

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

121-126

eissn

0167-5273

issn

1874-1754

pii

S0167-5273(18)36512-4

journal_volume

286

pub_type

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