Inflammasome activation: A keystone of proinflammatory response in obstructive sleep apnea
Rationale: As the mechanism that links obstructive sleep apnea (OSA) with the regulation of inflammatory response is not well known, it is important to understand the inflammasome activation, mainly of NLRP3 (nucleotide-binding oligomerization domain-like receptor 3). Objectives: To assess the NLRP3...
| Autores: | , , , , , , , , , , |
|---|---|
| Formato: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Recursos: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/737440 |
| Acesso em linha: | https://hdl.handle.net/10486/737440 https://dx.doi.org/10.1164/rccm.202106-1445OC |
| Access Level: | acceso abierto |
| Palavra-chave: | NLRP3 OSA Tissue factor HIF1α Intermittent hypoxia Medicina |
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Inflammasome activation: A keystone of proinflammatory response in obstructive sleep apneaDíaz García, ElenaGarcía Tovar, SaraAlfaro, EnriqueJaureguizar, AnaCasitas, RaquelSánchez Sánchez, BegoñaZamarrón, EsterFernández Lahera, JuanLópez Collado, EduardoCubillos Zapata, CarolinaGarcía Rio, FranciscoNLRP3OSATissue factorHIF1αIntermittent hypoxiaMedicinaRationale: As the mechanism that links obstructive sleep apnea (OSA) with the regulation of inflammatory response is not well known, it is important to understand the inflammasome activation, mainly of NLRP3 (nucleotide-binding oligomerization domain-like receptor 3). Objectives: To assess the NLRP3 activity in patients with severe OSA and to identify its role in the systemic inflammatory response of patients with OSA. Methods: We analyzed the NLRP3 activity as well as key components of the inflammasome cascade, such as adaptor molecule apoptosis-associated speck-like protein, caspase-1, Gasdermin D, IL-1β, IL-18, and tissue factor, in monocytes and plasma from patients with severe OSA and control subjects without sleep apnea. We explored the association of the different key markers with inflammatory comorbidities. Measurements and Main Results: Monocytes from patients with severe OSA presented higher NLRP3 activity than those from control subjects, which directly correlated with the apnea–hypopnea index and hypoxemic indices. NLRP3 overactivity triggered inflammatory cytokines (IL-1β and IL-18) via caspase-1 and increased Gasdermin D, allowing for tissue factor to be released. In vitro models confirmed that monocytes increase NLRP3 signaling under intermittent hypoxia in a hypoxia-inducible factor-1α–dependent manner, and/or in combination with plasma from patients with OSA. Plasma concentrations of tissue factor were higher in patients with OSA with systemic inflammatory comorbidities than in those without them. Conclusions: In patients with severe OSA, NLRP3 activation might be a linking mechanism between intermittent hypoxia and other OSA-induced immediate changes with the development of systemic inflammatory responseSupported by grants from Fondo de Investigación Sanitaria (FIS) and European Regional Development Funds (FEDER) (PI13/01512, PI16/00201, and PI19/01612 to F.G.-R. and CP18/00028 and PI19-01363 to C.C.-Z.)American Thoracic Society (ATS)Departamento de MedicinaFacultad de MedicinaGobierno de EspañaInstituto de Salud Carlos III20222022-06-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10486/737440https://dx.doi.org/10.1164/rccm.202106-1445OC35363597reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7374402026-06-23T12:46:27Z |
| dc.title.none.fl_str_mv |
Inflammasome activation: A keystone of proinflammatory response in obstructive sleep apnea |
| title |
Inflammasome activation: A keystone of proinflammatory response in obstructive sleep apnea |
| spellingShingle |
Inflammasome activation: A keystone of proinflammatory response in obstructive sleep apnea Díaz García, Elena NLRP3 OSA Tissue factor HIF1α Intermittent hypoxia Medicina |
| title_short |
Inflammasome activation: A keystone of proinflammatory response in obstructive sleep apnea |
| title_full |
Inflammasome activation: A keystone of proinflammatory response in obstructive sleep apnea |
| title_fullStr |
Inflammasome activation: A keystone of proinflammatory response in obstructive sleep apnea |
| title_full_unstemmed |
Inflammasome activation: A keystone of proinflammatory response in obstructive sleep apnea |
| title_sort |
Inflammasome activation: A keystone of proinflammatory response in obstructive sleep apnea |
| dc.creator.none.fl_str_mv |
Díaz García, Elena García Tovar, Sara Alfaro, Enrique Jaureguizar, Ana Casitas, Raquel Sánchez Sánchez, Begoña Zamarrón, Ester Fernández Lahera, Juan López Collado, Eduardo Cubillos Zapata, Carolina García Rio, Francisco |
| author |
Díaz García, Elena |
| author_facet |
Díaz García, Elena García Tovar, Sara Alfaro, Enrique Jaureguizar, Ana Casitas, Raquel Sánchez Sánchez, Begoña Zamarrón, Ester Fernández Lahera, Juan López Collado, Eduardo Cubillos Zapata, Carolina García Rio, Francisco |
| author_role |
author |
| author2 |
García Tovar, Sara Alfaro, Enrique Jaureguizar, Ana Casitas, Raquel Sánchez Sánchez, Begoña Zamarrón, Ester Fernández Lahera, Juan López Collado, Eduardo Cubillos Zapata, Carolina García Rio, Francisco |
| author2_role |
author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Departamento de Medicina Facultad de Medicina Gobierno de España Instituto de Salud Carlos III |
| dc.subject.none.fl_str_mv |
NLRP3 OSA Tissue factor HIF1α Intermittent hypoxia Medicina |
| topic |
NLRP3 OSA Tissue factor HIF1α Intermittent hypoxia Medicina |
| description |
Rationale: As the mechanism that links obstructive sleep apnea (OSA) with the regulation of inflammatory response is not well known, it is important to understand the inflammasome activation, mainly of NLRP3 (nucleotide-binding oligomerization domain-like receptor 3). Objectives: To assess the NLRP3 activity in patients with severe OSA and to identify its role in the systemic inflammatory response of patients with OSA. Methods: We analyzed the NLRP3 activity as well as key components of the inflammasome cascade, such as adaptor molecule apoptosis-associated speck-like protein, caspase-1, Gasdermin D, IL-1β, IL-18, and tissue factor, in monocytes and plasma from patients with severe OSA and control subjects without sleep apnea. We explored the association of the different key markers with inflammatory comorbidities. Measurements and Main Results: Monocytes from patients with severe OSA presented higher NLRP3 activity than those from control subjects, which directly correlated with the apnea–hypopnea index and hypoxemic indices. NLRP3 overactivity triggered inflammatory cytokines (IL-1β and IL-18) via caspase-1 and increased Gasdermin D, allowing for tissue factor to be released. In vitro models confirmed that monocytes increase NLRP3 signaling under intermittent hypoxia in a hypoxia-inducible factor-1α–dependent manner, and/or in combination with plasma from patients with OSA. Plasma concentrations of tissue factor were higher in patients with OSA with systemic inflammatory comorbidities than in those without them. Conclusions: In patients with severe OSA, NLRP3 activation might be a linking mechanism between intermittent hypoxia and other OSA-induced immediate changes with the development of systemic inflammatory response |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2022-06-01 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 AM http://purl.org/coar/version/c_ab4af688f83e57aa |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10486/737440 https://dx.doi.org/10.1164/rccm.202106-1445OC 35363597 |
| url |
https://hdl.handle.net/10486/737440 https://dx.doi.org/10.1164/rccm.202106-1445OC |
| identifier_str_mv |
35363597 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
American Thoracic Society (ATS) |
| publisher.none.fl_str_mv |
American Thoracic Society (ATS) |
| dc.source.none.fl_str_mv |
reponame:Biblos-e Archivo. Repositorio Institucional de la UAM instname:Universidad Autónoma de Madrid |
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Universidad Autónoma de Madrid |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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Biblos-e Archivo. Repositorio Institucional de la UAM |
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