Inflammasome Activation: A Keystone of Proinflammatory Response in Obstructive Sleep Apnea

Rationale: As the mechanism that links obstructive sleep apnea(OSA) with the regulation of inflammatory response is not wellknown, it is important to understand the inflammasomeactivation, mainly of NLRP3 (nucleotide-binding oligomerizationdomain-like receptor 3).Objectives: To assess the NLRP3 activity in patients with severeOSA and to identify its role in the systemic inflammatoryresponse of patients with OSA.Methods: We analyzed the NLRP3 activity as well askey components of the inflammasome cascade, such as adaptormolecule apoptosis-associated speck-like protein, caspase-1,Gasdermin D, IL-1b, IL-18, and tissue factor, in monocytesand plasma from patients with severe OSA and controlsubjects without sleep apnea. We explored theassociation of the different key markers with inflammatorycomorbidities.Measurements and Main Results: Monocytes from patientswith severe OSA presented higher NLRP3 activity than those fromcontrol subjects, which directly correlated with the apnea–hypopneaindex and hypoxemic indices. NLRP3 overactivity triggeredinflammatory cytokines (IL-1b and IL-18) via caspase-1 andincreased Gasdermin D, allowing for tissue factor to be released. Invitro models confirmed that monocytes increase NLRP3 signalingunder intermittent hypoxia in a hypoxia-inducible factor-1a–dependent manner, and/or in combination with plasma frompatients with OSA. Plasma concentrations of tissue factor werehigher in patients with OSA with systemic inflammatorycomorbidities than in those without them.Conclusions: In patients with severe OSA, NLRP3 activationmight be a linking mechanism between intermittent hypoxia andother OSA-induced immediate changes with the development ofsystemic inflammatory response.