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Neutrophil NLRP3 promotes cardiac injury following acute myocardial infarction through IL-1ß production, VWF release and NET deposition in the myocardium.
Heger, Lukas A; Schommer, Nicolas; Van Bruggen, Stijn; Sheehy, Casey E; Chan, William; Wagner, Denisa D.
Afiliación
  • Heger LA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, 1 Blackfan Circle, Ninth Floor, Boston, MA, 02115, USA.
  • Schommer N; Department of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA.
  • Van Bruggen S; Departement of Cardiology and Angiology, University Hospital Freiburg Bad Krozingen, 79106, Freiburg, Germany.
  • Sheehy CE; Program in Cellular and Molecular Medicine, Boston Children's Hospital, 1 Blackfan Circle, Ninth Floor, Boston, MA, 02115, USA.
  • Chan W; Departement of Cardiology and Angiology, University Hospital Freiburg Bad Krozingen, 79106, Freiburg, Germany.
  • Wagner DD; Program in Cellular and Molecular Medicine, Boston Children's Hospital, 1 Blackfan Circle, Ninth Floor, Boston, MA, 02115, USA.
Sci Rep ; 14(1): 14524, 2024 06 24.
Article en En | MEDLINE | ID: mdl-38914598
ABSTRACT
NLRP3 inflammasome has been implicated in neutrophil polarization and extrusion of neutrophil extracellular traps (NETs) in vitro and facilitates secretion of Il1-beta (IL-1ß). Permanent ligation of the left anterior descending artery was used to induce MI in WT and NLRP3-/- mice as well as in NLRP3-/- recipient mice transfused with either WT or NLRP3-/- neutrophils. NLRP3 deficiency reduced infarct size to roughly a third of WT heart injury and preserved left ventricular (LV) function at 12 h after MI as assessed by echocardiography and triphenyltetrazolium chloride staining of live tissue. Transfusion of WT but not NLRP3-/- neutrophils after MI increased infarct size in NLRP3-/- mice and significantly reduced LV function. The key features of myocardial tissue in WT neutrophil transfused recipients were increased H3Cit-positive deposits with NET-like morphology and increased tissue levels of IL-1ß and plasma levels of von Willebrand Factor (VWF). Flow cytometry analysis also revealed that neutrophil NLRP3 increased the number of labeled and transfused neutrophils in the bone marrow of recipient mice following MI. Our data suggest a key role for neutrophil NLRP3 in the production of IL-1ß and deposition of NETs in cardiac tissue exacerbating injury following MI. We provide evidence for a link between neutrophil NLRP3 and VWF release likely enhancing thromboinflammation in the heart. Neutrophil NLRP3 deficiency conferred similar cardioprotective effects to general NLRP3 deletion in MI rendering anti-neutrophil NLRP3 therapy a promising target for early cardioprotective treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de von Willebrand / Ratones Noqueados / Interleucina-1beta / Trampas Extracelulares / Proteína con Dominio Pirina 3 de la Familia NLR / Infarto del Miocardio / Miocardio / Neutrófilos Límite: Animals Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de von Willebrand / Ratones Noqueados / Interleucina-1beta / Trampas Extracelulares / Proteína con Dominio Pirina 3 de la Familia NLR / Infarto del Miocardio / Miocardio / Neutrófilos Límite: Animals Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido