Inflammasome activation mediated by oxidized LDL in patients with sleep apnea and early subclinical atherosclerosis.

Atherosclerosis is a common comorbidity of obstructive sleep apnea (OSA) patients, caused by the interaction of dyslipidemia and systemic inflammation. The OSA proinflammatory response is mediated by NLRP3 inflammasome activation, which requires a priming signal mediated by intermittent hypoxia and an activation signal provided by soluble stimulus present in plasma. Our objectives were to study the oxidized 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.We analyzed oxLDL, key components of the NLRP3 inflammasome cascade, and TF in plasma and monocytes from OSA patients and non-apneic 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.High levels of ox-LDL 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 intermittent hypoxia as a priming and activation signal of NLRP3 that enhances the inflammatory response, pyroptosis and TF release.In conclusion, OSA patients with eSA exhibit NLRP3 activation by intermittent hypoxia and the presence of ox-LDL capable of releasing TF, constituting a pathway for the interaction between dyslipidemia and systemic inflammation in the development of atherosclerotic lesions.