Inflammasome activation mediated by oxidised low-density lipoprotein in patients with sleep apnoea and early subclinical atherosclerosis

Background Atherosclerosis is a common comorbidity of obstructive sleep apnoea (OSA) patients, caused by the interaction of dyslipidaemia and systemic inflammation. The OSA pro-inflammatory response is mediated by NLRP3 inflammasome activation, which requires a priming signal mediated by intermitten...

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Autores: Díaz García, Elena, Sanz Rubio, David, García Tovar, Sara, Alfaro, Enrique, Cubero, Pablo, Gil, Ana V., Marín, José M., Cubillos Zapata, Carolina, García Rio, Francisco
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/737400
Acceso en línea:https://hdl.handle.net/10486/737400
https://dx.doi.org/10.1183/13993003.01401-2022
Access Level:acceso abierto
Palabra clave:NLRP3
sleep apnea
lipoproteins
Tissue Factor
Intermittent Hypoxia
Medicina
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spelling Inflammasome activation mediated by oxidised low-density lipoprotein in patients with sleep apnoea and early subclinical atherosclerosisDíaz García, ElenaSanz Rubio, DavidGarcía Tovar, SaraAlfaro, EnriqueCubero, PabloGil, Ana V.Marín, José M.Cubillos Zapata, CarolinaGarcía Rio, FranciscoNLRP3sleep apnealipoproteinsTissue FactorIntermittent HypoxiaMedicinaBackground Atherosclerosis is a common comorbidity of obstructive sleep apnoea (OSA) patients, caused by the interaction of dyslipidaemia and systemic inflammation. The OSA pro-inflammatory response is mediated by NLRP3 inflammasome activation, which requires a priming signal mediated by intermittent hypoxia (IH) and an activation signal provided by soluble stimulus present in plasma. Our objectives were to study oxidised low-density lipoprotein (oxLDL) expression in OSA patients with or without early subclinical atherosclerosis (eSA) as well as its contribution to NLRP3 activation and tissue factor (TF) release. Methods We analysed oxLDL, key components of the NLRP3 inflammasome cascade and TF in plasma and monocytes from OSA patients and non-apnoeic subjects, with or without eSA as determined by increased carotid intima–media thickness without the appearance of atherosclerotic plaques. The oxLDL contribution to NLRP3 inflammasome activation was assessed using in vitro models. Results High levels of oxLDL were identified in plasma from OSA patients, particularly in those with eSA, as well as an overexpression of NLRP3 cascade components and TF. Furthermore, in vitro models showed that both oxLDL and plasma from OSA patients with eSA act synergistically with IH as a priming and activation signal of NLRP3 that enhances the inflammatory response, pyroptosis and TF release. Conclusions OSA patients with eSA exhibit NLRP3 activation by IH and the presence of oxLDL capable of releasing TF, constituting a pathway for the interaction between dyslipidaemia and systemic inflammation in the development of atherosclerotic lesionsThis study was supported by grants from Fondo de Investigación Sanitaria (FIS) and European Regional Development Funds PI13/01512, PI16/00201 and PI19/01612 to F. García-Río, PI12/02175, PI15/01949 and PI18/01524 to J.M. Marin, and CP18/00028 and PI19-01363 to C. Cubillos-ZapataEuropean Respiratory Society (ERS)Departamento de MedicinaFacultad de MedicinaGobierno de EspañaInstituto de Salud Carlos III20232023-03-02research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10486/737400https://dx.doi.org/10.1183/13993003.01401-202236517180reponame: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:10486/7374002026-06-23T12:46:27Z
dc.title.none.fl_str_mv Inflammasome activation mediated by oxidised low-density lipoprotein in patients with sleep apnoea and early subclinical atherosclerosis
title Inflammasome activation mediated by oxidised low-density lipoprotein in patients with sleep apnoea and early subclinical atherosclerosis
spellingShingle Inflammasome activation mediated by oxidised low-density lipoprotein in patients with sleep apnoea and early subclinical atherosclerosis
Díaz García, Elena
NLRP3
sleep apnea
lipoproteins
Tissue Factor
Intermittent Hypoxia
Medicina
title_short Inflammasome activation mediated by oxidised low-density lipoprotein in patients with sleep apnoea and early subclinical atherosclerosis
title_full Inflammasome activation mediated by oxidised low-density lipoprotein in patients with sleep apnoea and early subclinical atherosclerosis
title_fullStr Inflammasome activation mediated by oxidised low-density lipoprotein in patients with sleep apnoea and early subclinical atherosclerosis
title_full_unstemmed Inflammasome activation mediated by oxidised low-density lipoprotein in patients with sleep apnoea and early subclinical atherosclerosis
title_sort Inflammasome activation mediated by oxidised low-density lipoprotein in patients with sleep apnoea and early subclinical atherosclerosis
dc.creator.none.fl_str_mv Díaz García, Elena
Sanz Rubio, David
García Tovar, Sara
Alfaro, Enrique
Cubero, Pablo
Gil, Ana V.
Marín, José M.
Cubillos Zapata, Carolina
García Rio, Francisco
author Díaz García, Elena
author_facet Díaz García, Elena
Sanz Rubio, David
García Tovar, Sara
Alfaro, Enrique
Cubero, Pablo
Gil, Ana V.
Marín, José M.
Cubillos Zapata, Carolina
García Rio, Francisco
author_role author
author2 Sanz Rubio, David
García Tovar, Sara
Alfaro, Enrique
Cubero, Pablo
Gil, Ana V.
Marín, José M.
Cubillos Zapata, Carolina
García Rio, Francisco
author2_role 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
sleep apnea
lipoproteins
Tissue Factor
Intermittent Hypoxia
Medicina
topic NLRP3
sleep apnea
lipoproteins
Tissue Factor
Intermittent Hypoxia
Medicina
description Background Atherosclerosis is a common comorbidity of obstructive sleep apnoea (OSA) patients, caused by the interaction of dyslipidaemia and systemic inflammation. The OSA pro-inflammatory response is mediated by NLRP3 inflammasome activation, which requires a priming signal mediated by intermittent hypoxia (IH) and an activation signal provided by soluble stimulus present in plasma. Our objectives were to study oxidised low-density lipoprotein (oxLDL) expression in OSA patients with or without early subclinical atherosclerosis (eSA) as well as its contribution to NLRP3 activation and tissue factor (TF) release. Methods We analysed oxLDL, key components of the NLRP3 inflammasome cascade and TF in plasma and monocytes from OSA patients and non-apnoeic subjects, with or without eSA as determined by increased carotid intima–media thickness without the appearance of atherosclerotic plaques. The oxLDL contribution to NLRP3 inflammasome activation was assessed using in vitro models. Results High levels of oxLDL were identified in plasma from OSA patients, particularly in those with eSA, as well as an overexpression of NLRP3 cascade components and TF. Furthermore, in vitro models showed that both oxLDL and plasma from OSA patients with eSA act synergistically with IH as a priming and activation signal of NLRP3 that enhances the inflammatory response, pyroptosis and TF release. Conclusions OSA patients with eSA exhibit NLRP3 activation by IH and the presence of oxLDL capable of releasing TF, constituting a pathway for the interaction between dyslipidaemia and systemic inflammation in the development of atherosclerotic lesions
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-03-02
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/10486/737400
https://dx.doi.org/10.1183/13993003.01401-2022
36517180
url https://hdl.handle.net/10486/737400
https://dx.doi.org/10.1183/13993003.01401-2022
identifier_str_mv 36517180
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 European Respiratory Society (ERS)
publisher.none.fl_str_mv European Respiratory Society (ERS)
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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