Background. Atherosclerosis is a frequent comorbidity of obstructive sleep apnea (OSA) patients, caused by the interaction of dyslipidemia and systemic inflammation. Recent data demonstrate that OSA pro-inflammatory response is mediated by NLRP3 activation. Interestingly, the recognition of oxidized low-density lipoprotein (oxLDL) plays a regulatory role in the NLRP3 inflammasome.

Aims and objectives. This work proposes to study the expression of oxLDL in OSA patients with or without early subclinical atherosclerosis (eSA) and its contribution to NLRP3 activation.

Methods. We analyzed oxLDL and NLRP3 components in plasma and leukocytes from OSA patients and non-apneic subjects, with or without eSA. 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 overexpression of NLRP3 cascade components. Furthermore, in vitro models showed that oxLDL present in plasma from OSA patients with eSA, through its receptor CD36, act synergistically with intermittent hypoxia as a priming and activation signal of the NLRP3 inflammasome, enhancing the inflammatory response and triggering pyroptosis. Finally, our results suggest a role of the NLRP3-pyroptosis axis in the release of tissue factor into plasma, which levels were higher in patients with eSA.

Conclusions. OSA patients with eSA exhibit NLRP3 activation mediated by intermittent hypoxia and the presence of high plasma oxLDL levels constituting a pathway for the interaction between dyslipidemia and systemic inflammation in the development of atherosclerotic lesions.