Sleep apnoea and immune regulation: The story is only beginning

Lam, David Cl; Ip, Mary S.M.

doi:10.1111/resp.13565

Cited by 2 publications

References 22 publications

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

Lee

Gulla

et al. 2020

Preprint

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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.

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

Lee

Gulla

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

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

Lee

Gulla

et al. 2021

eLife

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Obstructive sleep apnea (OSA) results from episodes of airway collapse and intermittent hypoxia (IH) and is associated with a host of health complications. Although the lung is the first organ to sense changes in oxygen levels, little is known about the consequences of IH to the lung hypoxia-inducible factor- (HIF)-responsive pathways. We hypothesized that exposure to IH would lead to cell-specific up and downregulation of diverse expression pathways. We identified changes in circadian and immune pathways in lungs from mice exposed to IH. Among all cell types, endothelial cells showed the most prominent transcriptional changes. Upregulated genes in myofibroblast cells were enriched for genes associated with pulmonary hypertension and included targets of several drugs currently used to treat chronic pulmonary diseases. A better understanding of the pathophysiologic mechanisms underlying diseases associated with OSA could improve our therapeutic approaches, directing therapies to the most relevant cells and molecular pathways.

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Sleep apnoea and immune regulation: The story is only beginning

Abstract: See related https://onlinelibrary.wiley.com/doi/10.1111/resp.13470

Cited by 2 publications

References 22 publications

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

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

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

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