Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain.
Respiratory Diseases Group, Respiratory Service, and.
Am J Respir Crit Care Med. 2022 Jun 1;205(11):1337-1348. doi: 10.1164/rccm.202106-1445OC.
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). To assess the NLRP3 activity in patients with severe OSA and to identify its role in the systemic inflammatory response of patients with OSA. 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. 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 control subjects, which directly correlated with the apnea-hypopnea index and hypoxemic indices. NLRP3 overactivity triggered inflammatory cytokines (IL-1β and IL-18) via caspase-1 and increased Gasdermin D, allowing for tissue factor to be released. 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. 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.
由于阻塞性睡眠呼吸暂停（OSA）与炎症反应调节的机制尚不清楚，因此了解炎症小体的激活（主要是 NLRP3）非常重要。评估严重 OSA 患者的 NLRP3 活性，并确定其在 OSA 患者全身炎症反应中的作用。我们分析了严重 OSA 患者和无睡眠呼吸暂停的对照组患者单核细胞和血浆中的 NLRP3 活性以及炎症小体级联的关键成分，如衔接蛋白凋亡相关斑点样蛋白、半胱天冬酶-1、Gasdermin D、IL-1β、IL-18 和组织因子。我们探讨了不同关键标志物与炎症合并症的相关性。严重 OSA 患者的单核细胞的 NLRP3 活性高于对照组，这与呼吸暂停-低通气指数和低氧指数直接相关。NLRP3 过度活跃通过半胱天冬酶-1触发炎症细胞因子（IL-1β 和 IL-18），并增加 Gasdermin D，从而允许组织因子释放。模型证实，单核细胞在间歇性低氧下通过缺氧诱导因子-1α 依赖性方式或与 OSA 患者的血浆联合增加 NLRP3 信号，血浆组织因子浓度在伴有全身炎症合并症的 OSA 患者中高于无合并症者。在严重 OSA 患者中，NLRP3 激活可能是间歇性低氧与其他 OSA 诱导的即时变化之间的联系机制，导致全身炎症反应的发展。
