Portal de investigación
miR-146a is a pivotal regulator of neutrophil extracellular trap formation promoting thrombosis.
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Arroyo AB
- Fernández-Pérez MP
- Del Monte A
- Águila S
- Hernández-Antolín R
- García-Barber N
- de Los Reyes-García AM
- Arcas MI
- Vicente V
- Andrés V
- González-Conejero R
- Martínez C
Grupos
Abstract
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.
Datos de la publicación
- ISSN/ISSNe:
- 0390-6078, 1592-8721
- Tipo:
- Article
- Páginas:
- 1636-1646
- PubMed:
- 32586906
- Factor de Impacto:
- 2,528 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
HAEMATOLOGICA FERRATA STORTI FOUNDATION
Citas Recibidas en Web of Science: 52
Documentos
- No hay documentos
Filiaciones
Keywords
- Arterial Thrombosis, Atherosclerosis, NETosis, miR-146a, sepsis
Campos de Estudio
Cita
Arroyo AB,Fernández MP,Del Monte A,Águila S,MÉNDEZ R,Hernández R,García N,de Los Reyes AM,GONZÁLEZ P,Arcas MI,Vicente V,MENÉNDEZ R,Andrés V,González R,Martínez C. miR-146a is a pivotal regulator of neutrophil extracellular trap formation promoting thrombosis. Haematologica. 2021. 106. (6):p. 1636-1646. IF:11,049. (1).