Short-term exposure to intermittent hypoxia in mice leads to changes in gene expression seen in chronic pulmonary disease

Obstructive sleep apnea (OSA) results from intermittent episodes of airway collapse and hypoxia and is associated with a host of health complications including dementia, diabetes, heart failure, and stroke. Cellular mechanisms causing disease progression across multiple systems in OSA are unknown. Although it is known that pulmonary diseases share general mechanisms, such as systemic inflammation and oxidative stress, there is an incomplete understanding of the early-stage changes to the lung from OSA. Using intermittent hypoxia (IH) as a mouse model of OSA, we showed profound cell-type specific changes in genome-wide expression in the lung. With single-cell RNA analysis, we identified substantial similarities between lungs of mice exposed to IH and human lung tissue from patients with pulmonary disease––most notably pulmonary hypertension, COPD, and asthma. Many IH-responsive genes encode targets of drugs currently available to treat pulmonary disease. Present data provide insights into the initiation of specific cellular responses which drive disease progression in a model of OSA. This information can help direct therapies to the most relevant cells and molecular pathways.