Abstract
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.
Abstract
Oxidised low-density lipoprotein (oxLDL) may play a key role in NLRP3 inflammasome activation in OSA patients leading to tissue factor release, a recognised mediator of atherosclerosis and atherothrombosis development. https://bit.ly/3zzHo1n
Footnotes
Conflict of interest: All authors have nothing to disclose.
Support statement: This 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-Zapata. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received July 11, 2022.
- Accepted October 20, 2022.
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