American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jun 2022
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 well known, it is important to understand the inflammasome activation, mainly of NLRP3 (nucleotide-binding oligomerization domain-like receptor 3). Objectives: To assess the NLRP3 activity in patients with severe OSA and to identify its role in the systemic inflammatory response of patients with OSA. Methods: We analyzed the NLRP3 activity as well as key components of the inflammasome cascade, such as adaptor molecule apoptosis-associated speck-like protein, caspase-1, Gasdermin D, IL-1β, IL-18, and tissue factor, in monocytes and plasma from patients with severe OSA and control subjects without sleep apnea. ⋯ In vitro models confirmed that monocytes increase NLRP3 signaling under intermittent hypoxia in a hypoxia-inducible factor-1α-dependent manner, and/or in combination with plasma from patients with OSA. Plasma concentrations of tissue factor were higher in patients with OSA with systemic inflammatory comorbidities than in those without them. Conclusions: In patients with severe OSA, NLRP3 activation might be a linking mechanism between intermittent hypoxia and other OSA-induced immediate changes with the development of systemic inflammatory response.