Different Effects of Acute and Chronic Hypoxia on Antiviral Capacity of Pulmonary Vascular Endothelial Cells.

Asthma and chronic obstructive pulmonary disease (COPD) are chronic respiratory diseases associated with inflammation and structural changes in the airways. Hypoxia is a key element of the pulmonary microenvironment, particularly in obstructive diseases, where it can be transient (e.g., during asthma exacerbations) or chronic (COPD). Pulmonary vascular endothelial cells (ECs) are important components of the immune response and (like the epithelium) are exposed to hypoxia and viral infections. Although it has been demonstrated that ECs can be infected by respiratory viruses and that hypoxia can affect their function, the impact of hypoxia on the antiviral capabilities of the endothelium remains poorly understood. This study examined the influence of acute and chronic hypoxia on the antiviral properties of human lung microvascular ECs. Acute and chronic hypoxia upregulated endosomal RNA receptors TLR3 and TLR7, whereas they downregulated cytosolic RIG-I and MDA5. Acute hypoxia downregulated mRNA and protein expression of IRF3 and IRF7 and inhibited effector antiviral mechanisms, whereas chronic hypoxia induced IRF7, OAS-1, protein kinase-R (PKR), and Mx1 at both mRNA and protein levels by flow cytometry. In addition, both hypoxia models caused increased secretion of lymphocyte-recruiting chemokines, whereas the secretion of cytokines/chemokines responsible for the involvement of monocytes and macrophages was inhibited. Acute hypoxia suppresses antiviral regulatory and effector pathways, whereas chronic hypoxia enhances viral RNA detection and intracellular antiviral mechanisms. These findings highlight the complex role of hypoxia in shaping endothelial immune responses and suggest that, depending on its duration, it may influence susceptibility to viral infections in chronic respiratory diseases.