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

Díaz-García, E. ; Sanz-Rubio, D. ; García-Tovar, S. ; Alfaro, E. ; Cubero, P. ; Gil, A. V. ; Marín, J. M. (Universidad de Zaragoza) ; Cubillos-Zapata, C. ; García-Río, F.

Resumen: 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.MethodsWe 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 usingin vitromodels.ResultsHigh 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 vitromodels 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.ConclusionsOSA 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.

Idioma: Inglés

DOI: 10.1183/13993003.01401-2022

Año: 2023

Publicado en: European respiratory journal 61, 3 (2023), 2201401 [33 pp.]
ISSN: 0903-1936

Factor impacto JCR: 17.0 (2023)

Categ. JCR: RESPIRATORY SYSTEM rank: 4 / 101 = 0.04 (2023) - Q1 - T1

Factor impacto CITESCORE: 27.5 - Pulmonary and Respiratory Medicine (Q1)

Factor impacto SCIMAGO: 3.81 - Pulmonary and Respiratory Medicine (Q1) - Medicine (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/FIS/PI13-01512
Financiación: info:eu-repo/grantAgreement/ES/FIS/PI15-01949
Financiación: info:eu-repo/grantAgreement/ES/FIS/PI16-00201
Financiación: info:eu-repo/grantAgreement/ES/FIS/PI18-00028
Financiación: info:eu-repo/grantAgreement/ES/FIS/PI18-01363
Financiación: info:eu-repo/grantAgreement/ES/FIS/PI19-01612
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-FEDER-FIS/PI18-01524
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI12-02175

Tipo y forma: Article (Published version)

Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)