The NLRP3 inflammasome in alveolar macrophages promotes angiogenesis in intermittent short-duration reoxygenation which relieves chronic hypoxic pulmonary hypertension

Abstract High altitude pulmonary hypertension (HAPH) is a chronic progressive disease caused by the reconstruction of distal pulmonary arterioles caused by chronic hypoxia. Due to the limited effect of current protective measures for treating HAPH, we propose the use of intermittent short-duration reoxygenation and prove its effectiveness in protecting against HAPH in an animal model. However, the mechanism of relieving HAPH by intermittent short-duration reoxygenation still needs to be further clarified. Previous studies have shown that alveolar macrophages and the inflammatory response induced by the NLRP3 inflammasome play an important role in the development of hypoxic pulmonary hypertension. However, repeated hypoxia and reoxygenation may lead to increased levels of inflammation due to increased oxidative stress. Therefore, the purpose of this study was to examine the changes in alveolar macrophages and the NLRP3 inflammasome under intermittent short-duration reoxygenation and their role in the protective effect. The results showed that intermittent short-duration reoxygenation resulted in higher density of pulmonary vessel bed and higher expression of the NLRP3 inflammasome in lung tissues and alveolar macrophages than continuous hypoxia. In addition, the depletion of alveolar macrophages or inhibition of the NLRP3 inflammasome in the lung counteracted the protective effect of intermittent short-duration reoxygenation on HAPH. Based on these results, we suggest that alveolar macrophages and the NLRP3 inflammasome promote angiogenesis in intermittent short-duration reoxygenation-mediated protection against HAPH.