Obstructive sleep apnea in a mouse model is associated with tissue-specific transcriptomic changes in circadian rhythmicity and mean 24-hour gene expression.
Intermittent hypoxia (IH) is a major clinical feature of obstructive sleep apnea (OSA). The mechanisms that become dysregulated after periods of exposure to IH are unclear, particularly in the early stages of disease. The circadian clock governs a wide array of biological functions and is intimately...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-05-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3002139 |
| _version_ | 1797812060468281344 |
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| author | Bala S C Koritala Yin Yeng Lee Laetitia S Gaspar Shweta S Bhadri Wen Su Gang Wu Lauren J Francey Marc D Ruben Ming C Gong John B Hogenesch David F Smith |
| author_facet | Bala S C Koritala Yin Yeng Lee Laetitia S Gaspar Shweta S Bhadri Wen Su Gang Wu Lauren J Francey Marc D Ruben Ming C Gong John B Hogenesch David F Smith |
| author_sort | Bala S C Koritala |
| collection | DOAJ |
| description | Intermittent hypoxia (IH) is a major clinical feature of obstructive sleep apnea (OSA). The mechanisms that become dysregulated after periods of exposure to IH are unclear, particularly in the early stages of disease. The circadian clock governs a wide array of biological functions and is intimately associated with stabilization of hypoxia-inducible factors (HIFs) under hypoxic conditions. In patients, IH occurs during the sleep phase of the 24-hour sleep-wake cycle, potentially affecting their circadian rhythms. Alterations in the circadian clock have the potential to accelerate pathological processes, including other comorbid conditions that can be associated with chronic, untreated OSA. We hypothesized that changes in the circadian clock would manifest differently in those organs and systems known to be impacted by OSA. Using an IH model to represent OSA, we evaluated circadian rhythmicity and mean 24-hour expression of the transcriptome in 6 different mouse tissues, including the liver, lung, kidney, muscle, heart, and cerebellum, after a 7-day exposure to IH. We found that transcriptomic changes within cardiopulmonary tissues were more affected by IH than other tissues. Also, IH exposure resulted in an overall increase in core body temperature. Our findings demonstrate a relationship between early exposure to IH and changes in specific physiological outcomes. This study provides insight into the early pathophysiological mechanisms associated with IH. |
| first_indexed | 2024-03-13T07:32:59Z |
| format | Article |
| id | doaj.art-e04c4b5965044dc0abdef46011780cda |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-03-13T07:32:59Z |
| publishDate | 2023-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-e04c4b5965044dc0abdef46011780cda2023-06-04T05:31:11ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852023-05-01215e300213910.1371/journal.pbio.3002139Obstructive sleep apnea in a mouse model is associated with tissue-specific transcriptomic changes in circadian rhythmicity and mean 24-hour gene expression.Bala S C KoritalaYin Yeng LeeLaetitia S GasparShweta S BhadriWen SuGang WuLauren J FranceyMarc D RubenMing C GongJohn B HogeneschDavid F SmithIntermittent hypoxia (IH) is a major clinical feature of obstructive sleep apnea (OSA). The mechanisms that become dysregulated after periods of exposure to IH are unclear, particularly in the early stages of disease. The circadian clock governs a wide array of biological functions and is intimately associated with stabilization of hypoxia-inducible factors (HIFs) under hypoxic conditions. In patients, IH occurs during the sleep phase of the 24-hour sleep-wake cycle, potentially affecting their circadian rhythms. Alterations in the circadian clock have the potential to accelerate pathological processes, including other comorbid conditions that can be associated with chronic, untreated OSA. We hypothesized that changes in the circadian clock would manifest differently in those organs and systems known to be impacted by OSA. Using an IH model to represent OSA, we evaluated circadian rhythmicity and mean 24-hour expression of the transcriptome in 6 different mouse tissues, including the liver, lung, kidney, muscle, heart, and cerebellum, after a 7-day exposure to IH. We found that transcriptomic changes within cardiopulmonary tissues were more affected by IH than other tissues. Also, IH exposure resulted in an overall increase in core body temperature. Our findings demonstrate a relationship between early exposure to IH and changes in specific physiological outcomes. This study provides insight into the early pathophysiological mechanisms associated with IH.https://doi.org/10.1371/journal.pbio.3002139 |
| spellingShingle | Bala S C Koritala Yin Yeng Lee Laetitia S Gaspar Shweta S Bhadri Wen Su Gang Wu Lauren J Francey Marc D Ruben Ming C Gong John B Hogenesch David F Smith Obstructive sleep apnea in a mouse model is associated with tissue-specific transcriptomic changes in circadian rhythmicity and mean 24-hour gene expression. PLoS Biology |
| title | Obstructive sleep apnea in a mouse model is associated with tissue-specific transcriptomic changes in circadian rhythmicity and mean 24-hour gene expression. |
| title_full | Obstructive sleep apnea in a mouse model is associated with tissue-specific transcriptomic changes in circadian rhythmicity and mean 24-hour gene expression. |
| title_fullStr | Obstructive sleep apnea in a mouse model is associated with tissue-specific transcriptomic changes in circadian rhythmicity and mean 24-hour gene expression. |
| title_full_unstemmed | Obstructive sleep apnea in a mouse model is associated with tissue-specific transcriptomic changes in circadian rhythmicity and mean 24-hour gene expression. |
| title_short | Obstructive sleep apnea in a mouse model is associated with tissue-specific transcriptomic changes in circadian rhythmicity and mean 24-hour gene expression. |
| title_sort | obstructive sleep apnea in a mouse model is associated with tissue specific transcriptomic changes in circadian rhythmicity and mean 24 hour gene expression |
| url | https://doi.org/10.1371/journal.pbio.3002139 |
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