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

As the mechanism that links obstructive sleep apnea (OSA) with the regulation of inflammatory response is not well known, it is important to understand the inflammasome activation, mainly of nucleotide-binding oligomerization domain-like receptor 3 (NLRP3).To assess the NLRP3 activity in severe OSA patients and to identify its role in the systemic inflammatory response of OSA patients.We analyzed the NLRP3 activity as well as key components of the inflammasome cascade, such as adaptor molecule apoptosis-associated speck-like protein (ASC), caspase-1, Gasdermin D (GSDMD), interleukin (IL)-1β, IL-18 and tissue factor (TF), in monocytes and plasma from patients with severe OSA and non-apneic healthy subjects. We explored the association of the different key markers with inflammatory comorbidities.Monocytes from patients with severe OSA presented higher NLRP3 activity than those from non-apneic control subjects, which directly correlated with the apnea-hypopnea index and hypoxemic indices. NLRP3 over-activity triggered inflammatory cytokines (Il-1β and IL-18) via caspase-1 and increased Gasdermin D, allowing for tissue factor to be released. In vitro models confirmed that monocytes increase NLRP3 signaling under intermittent hypoxia (IH) in an HIF-1α-dependent manner, and/or in combination with plasma from OSA patients. Plasma levels of TF were higher in OSA patients with systemic inflammatory comorbidities than in those without them.In severe OSA patients, NLRP3 activation might be a linking mechanism between intermittent hypoxia and other OSA-induced immediate changes with the development of systemic inflammatory response.