2026-04-26T23:30:33Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/133782024-11-29T11:04:59Zcom_20.500.12105_19604com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19605col_20.500.12105_16981

00925njm 22002777a 4500 dc Arroyo, Ana B author Fernandez-Perez, Maria P author del Monte, Alberto author Aguila, Sonia author Mendez, Raul author Hernandez-Antolin, Rebecca author Garcia-Barber, Nuria author de Los Reyes-Garcia, Ascension M author Gonzalez-Jimenez, Paula author Arcas, Maria I author Vicente, Vicente author Menendez, Rosario author Andres, Vicente author Gonzalez-Conejero, Rocio author Martinez, Constantino author 2021-06 Neutrophil extracellular traps (NETs) induce a procoagulant response linking inflammation and thrombosis. Low levels of miR-146a, a brake of inflammatory response, are involved in higher risk for cardiovascular events, but the mechanisms explaining how miR-146a exerts its function remain largely undefined. The aim of this study was to explore the impact of miR-146a deficiency in NETosis both, in sterile and non-sterile models in vivo, and to inquire into the underlying mechanism. Two models of inflammation were performed: 1) Ldlr-/- mice transplanted with bone marrow from miR-146a-/- or wild type (WT) were fed high-fat diet, generating an atherosclerosis model; and 2) an acute inflammation model was generated by injecting lipopolysaccharide (LPS) (1 mg/Kg) into miR-146a-/- and WT mice. miR-146a deficiency increased NETosis in both models. Accordingly, miR-146a-/- mice showed significant reduced carotid occlusion time and elevated levels of NETs in thrombi following FeCl3-induced thrombosis. Infusion of DNAse I abolished arterial thrombosis in WT and miR-146a-/- mice. Interestingly, miR-146a deficient mice have aged, hyperreactive and pro-inflammatory neutrophils in circulation that are more prone to form NETs independently of the stimulus. Furthermore, we demonstrated that community acquired pneumonia (CAP) patients with reduced miR-146a levels associated with the T variant of the functional rs2431697, presented an increased risk for cardiovascular events due in part to an increased generation of NETs. Haematologica. 2021; 106(6):1636-1646 1592-8721 http://hdl.handle.net/20.500.12105/13378 32586906 10.3324/haematol.2019.240226 Haematologica miR-146a is a pivotal regulator of neutrophil extracellular trap formation promoting thrombosis.