Orosomucoid 1 Participates in Alveolar Hypercoagulation and Fibrinolytic Inhibition Involving NF-κB Signaling Pathway...

Alveolar hypercoagulation and fibrinolytic inhibition are key drivers of refractory hypoxemia in acute respiratory distress syndrome (ARDS). Orosomucoid 1 (ORM1), associated with coagulation and the NF-κB pathway, is hypothesized to regulate these processes in ARDS via NF-κB. By using LPS-induced ARDS rats and alveolar epithelial type II (AEC II) cells, we measured ORM1 expression and its effects on tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1). NF-κB pathway involvement was assessed. Clinically, bronchoalveolar lavage fluid (BALF) ORM1 levels and their correlation with TF/PAI-1 were analyzed in ARDS patients. In ARDS rats, ORM1 was upregulated in lung tissue and BALF, correlating with increased TF, PAI-1, and type III collagen. In vitro, ORM1 promoted TF and PAI-1 expression in LPS-stimulated AEC II cells. These effects were mediated through the NF-κB pathway. Clinically, BALF ORM1 levels were elevated in ARDS patients and positively correlated with TF and PAI-1. ORM1 regulates alveolar hypercoagulation and fibrinolytic inhibition in LPS-induced ARDS via the NF-κB pathway, identifying it as a promising therapeutic target.