Regadenoson Inhibits the Formation of Neutrophil Extracellular Traps, Alleviating Endothelial Injury Caused by Decompression Sickness

Background: Decompression sickness (DCS) is a common condition found in divers. However, the role of neutrophil extracellular traps (NETs) in the development of DCS is still unknown. This study sought to investigate the underlying mechanism of endothelial injury caused by NETs. Methods: A DCS mouse model was developed to assess the therapeutic effect of regadenoson (a selective A2A adenosine receptor agonist) in these models. The mice were divided into three groups: the control, model, and model+regadenoson (REG) groups. The DCS mouse model was established by applying a computer -controlled steel hyperbaric oxygen chamber to create a DCSlike environment. Moreover, the histopathological score of the lung tissues excised from treated mice was determined using Hematoxylin and Eosin (H&E) staining. Furthermore, the levels of tumor necrosis factor alpha (TNF-alpha), interleukin-10 (IL -10), IL -16, IL -13, and IL-1 beta were evaluated using Real-time PCR. NETs were assessed using the double fluorescence staining method. Additionally, the activation levels of the phosphatidylinositol-3 kinase/a serine/threonine protein kinase (PI3K/AKT) signaling pathway were determined using Western blot analysis. Results: We found that regadenoson contributed to reducing lung inflammation and vascular endothelial injury. Additionally, regadenoson activated A2A receptors and upregulated the expression of prefoldin subunit 6 (PFDN6) protein (p < 0.05), thereby suppressing the formation of NETs. Moreover, NETs adversely affected the viability, and migration ability and caused cellular injury of endothelial cells by inhibiting a serine/threonine protein kinase (AKT) signaling pathway. However, regadenoson interrupted this effect by suppressing the formation of NETs. Moreover, regadenoson significantly reduced lung inflammation and endothelial damage (p < 0.05). Conclusions: Regadenoson holds promising potential in treating DCS.