Yangxia Xua, Xiue Pangba
Tiantai County People’s Hospital.
China
Experimental Lung Research
Exp Lung Res 2026; 52: 196–206
DOI: 10.1080/01902148.2026.2704400
Abstract
Objective: To investigate the mechanism by which Intermittent Hypoxia (IH) promotes Pulmonary Arterial Hypertension (PAH), focusing on ROS-NLRP3 inflammasome-mediated endothelial cell pyroptosis.
Methods: Human Pulmonary Microvascular Endothelial Cells (HPMECs) and a monocrotaline-induced PAH rat model were exposed to an IH environment. Interventions included the ROS inhibitor N-acetylcysteine (NAC) and the NLRP3 inhibitor MCC950. Assessments measured cell survival, LDH activity, ROS levels, apoptosis, inflammatory cytokines (IL-1β, IL-18), and protein expression of NLRP3 inflammasome components. In rats, hemodynamics, right ventricular hypertrophy, and pulmonary vascular remodeling were evaluated.
Results: IH exposure significantly decreased HPMEC survival and increased LDH activity, ROS levels, apoptosis rate, and the expression of NLRP3, Caspase-1, and ASC proteins. These effects, along with elevated IL-1β and IL-18, were reversed by NAC and MCC950 treatment. In PAH rats, IH exacerbated right ventricular systolic pressure, pulmonary artery pressure, vascular remodeling, and serum inflammatory markers, which were similarly ameliorated by NAC and MCC950.
Conclusion: IH promotes the progression of PAH by inducing endothelial cell pyroptosis through the activation of the ROS-NLRP3 inflammasome pathway.
Category
Class I. Drug-induced and Toxin-induced Pulmonary Hypertension
Class III. Pulmonary Hypertension Associated with Alveolar Hypoxia
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Animal Models of Pulmonary Vascular Disease and Therapy
Pulmonary Vascular Pathology
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes