Editorial

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Open AccessEditorial

Editorial to Special Issue “Sleep Apnea and Intermittent Hypoxia 2.0”

by Shin Takasawa

Int. J. Mol. Sci. 2022, 23(10), 5299; https://doi.org/10.3390/ijms23105299 - 10 May 2022

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Sleep apnea syndrome (SAS) is the most common form of sleep-disordered breathing and is associated with many adverse health consequences, including increased overall mortality risk [...] Full article

(This article belongs to the Special Issue Sleep Apnea and Intermittent Hypoxia 2.0)

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Research

Jump to: Editorial, Review

13 pages, 1727 KiB

Open AccessArticle

Elevated Monocytic Interleukin-8 Expression under Intermittent Hypoxia Condition and in Obstructive Sleep Apnea Patients

by Li-Pang Chuang, Huang-Pin Wu, Li-Ang Lee, Li-Chung Chiu, Shih-Wei Lin, Han-Chung Hu, Kuo-Chin Kao, Ning-Hung Chen, Jung-Wei Tsai and Jong-Hwei Su Pang

Int. J. Mol. Sci. 2021, 22(21), 11396; https://doi.org/10.3390/ijms222111396 - 22 Oct 2021

Cited by 3 | Viewed by 1871

Abstract

Obstructive sleep apnea (OSA) is a disease with great cardiovascular risk. Interleukin-8 (IL-8), an important chemokine for monocyte chemotactic migration, was studied under intermittent hypoxia condition and in OSA patients. Monocytic THP-1 cells were used to investigate the effect of intermittent hypoxia on [...] Read more.

Obstructive sleep apnea (OSA) is a disease with great cardiovascular risk. Interleukin-8 (IL-8), an important chemokine for monocyte chemotactic migration, was studied under intermittent hypoxia condition and in OSA patients. Monocytic THP-1 cells were used to investigate the effect of intermittent hypoxia on the regulation of IL-8 by an intermittent hypoxic culture system. The secreted protein and mRNA levels were studied by means of enzyme-linked immunosorbent assay and RT/real-time PCR. The chemotactic migration of monocytes toward a conditioned medium containing IL-8 was performed by means of the transwell filter migration assay. Peripheral venous blood was collected from 31 adult OSA patients and RNA was extracted from the monocytes for the analysis of IL-8 expression. The result revealed that intermittent hypoxia enhanced the monocytic THP-1 cells to actively express IL-8 at both the secreted protein and mRNA levels, which subsequently increased the migration ability of monocytes toward IL-8. The ERK, PI3K and PKC pathways were demonstrated to contribute to the activation of IL-8 expression by intermittent hypoxia. In addition, increased monocytic IL-8 expression was found in OSA patients, with disease severity dependence and diurnal changes. This study concluded the monocytic IL-8 gene expression can be activated by intermittent hypoxia and increased in OSA patients. Full article

(This article belongs to the Special Issue Sleep Apnea and Intermittent Hypoxia 2.0)

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16 pages, 2687 KiB

Open AccessArticle

Intermittent Hypoxia Upregulates the Renin and Cd38 mRNAs in Renin-Producing Cells via the Downregulation of miR-203

by Yoshinori Takeda, Asako Itaya-Hironaka, Akiyo Yamauchi, Mai Makino, Sumiyo Sakuramoto-Tsuchida, Hiroyo Ota, Ryuji Kawaguchi and Shin Takasawa

Int. J. Mol. Sci. 2021, 22(18), 10127; https://doi.org/10.3390/ijms221810127 - 19 Sep 2021

Cited by 14 | Viewed by 2476

Abstract

Sleep apnea syndrome is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]), and it is a known risk factor for hypertension. The upregulation of the renin-angiotensin system has been reported in IH, and the correlation between renin and CD38 [...] Read more.

Sleep apnea syndrome is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]), and it is a known risk factor for hypertension. The upregulation of the renin-angiotensin system has been reported in IH, and the correlation between renin and CD38 has been noted. We exposed human HEK293 and mouse As4.1 renal cells to experimental IH or normoxia for 24 h and then measured the mRNA levels using a real-time reverse transcription polymerase chain reaction. The mRNA levels of Renin (Ren) and Cd38 were significantly increased by IH, indicating that they could be involved in the CD38-cyclic ADP-ribose signaling pathway. We next investigated the promotor activities of both genes, which were not increased by IH. Yet, a target mRNA search of the microRNA (miRNA) revealed both mRNAs to have a potential target sequence for miR-203. The miR-203 level of the IH-treated cells was significantly decreased when compared with the normoxia-treated cells. The IH-induced upregulation of the genes was abolished by the introduction of the miR-203 mimic, but not the miR-203 mimic NC negative control. These results indicate that IH stress downregulates the miR-203 in renin-producing cells, thereby resulting in increased mRNA levels of Ren and Cd38, which leads to hypertension. Full article

(This article belongs to the Special Issue Sleep Apnea and Intermittent Hypoxia 2.0)

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Review

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13 pages, 1037 KiB

Open AccessReview

Anorexigenic Effects of Intermittent Hypoxia on the Gut—Brain Axis in Sleep Apnea Syndrome

by Ryogo Shobatake, Hiroyo Ota, Nobuyuki Takahashi, Satoshi Ueno, Kazuma Sugie and Shin Takasawa

Int. J. Mol. Sci. 2022, 23(1), 364; https://doi.org/10.3390/ijms23010364 - 29 Dec 2021

Cited by 5 | Viewed by 2278

Abstract

Sleep apnea syndrome (SAS) is a breathing disorder characterized by recurrent episodes of upper-airway collapse, resulting in intermittent hypoxia (IH) during sleep. Experimental studies with animals and cellular models have indicated that IH leads to attenuation of glucose-induced insulin secretion from pancreatic β [...] Read more.

Sleep apnea syndrome (SAS) is a breathing disorder characterized by recurrent episodes of upper-airway collapse, resulting in intermittent hypoxia (IH) during sleep. Experimental studies with animals and cellular models have indicated that IH leads to attenuation of glucose-induced insulin secretion from pancreatic β cells and to enhancement of insulin resistance in peripheral tissues and cells, such as the liver (hepatocytes), adipose tissue (adipocytes), and skeletal muscles (myocytes), both of which could lead to obesity. Although obesity is widely recognized as a major factor in SAS, it is controversial whether the development of SAS could contribute directly to obesity, and the effect of IH on the expression of appetite regulatory genes remains elusive. Appetite is regulated appropriately by both the hypothalamus and the gut as a gut–brain axis driven by differential neural and hormonal signals. In this review, we summarized the recent epidemiological findings on the relationship between SAS and feeding behavior and focused on the anorexigenic effects of IH on the gut–brain axis by the IH-induced up-regulation of proopiomelanocortin and cocaine- and amphetamine-regulated transcript in neuronal cells and the IH-induced up-regulation of peptide YY, glucagon-like peptide-1 and neurotensin in enteroendocrine cells and their molecular mechanisms. Full article

(This article belongs to the Special Issue Sleep Apnea and Intermittent Hypoxia 2.0)

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15 pages, 1343 KiB

Open AccessReview

Effects of Intermittent Hypoxia on Cytokine Expression Involved in Insulin Resistance

by Tomoko Uchiyama, Hiroyo Ota, Chiho Ohbayashi and Shin Takasawa

Int. J. Mol. Sci. 2021, 22(23), 12898; https://doi.org/10.3390/ijms222312898 - 29 Nov 2021

Cited by 11 | Viewed by 2777

Abstract

Sleep apnea syndrome (SAS) is a prevalent disorder characterized by recurrent apnea or hypoxia episodes leading to intermittent hypoxia (IH) and arousals during sleep. Currently, the relationship between SAS and metabolic diseases is being actively analyzed, and SAS is considered to be an [...] Read more.

Sleep apnea syndrome (SAS) is a prevalent disorder characterized by recurrent apnea or hypoxia episodes leading to intermittent hypoxia (IH) and arousals during sleep. Currently, the relationship between SAS and metabolic diseases is being actively analyzed, and SAS is considered to be an independent risk factor for the development and progression of insulin resistance/type 2 diabetes (T2DM). Accumulating evidence suggests that the short cycles of decreased oxygen saturation and rapid reoxygenation, a typical feature of SAS, contribute to the development of glucose intolerance and insulin resistance. In addition to IH, several pathological conditions may also contribute to insulin resistance, including sympathetic nervous system hyperactivity, oxidative stress, vascular endothelial dysfunction, and the activation of inflammatory cytokines. However, the detailed mechanism by which IH induces insulin resistance in SAS patients has not been fully revealed. We have previously reported that IH stress may exacerbate insulin resistance/T2DM, especially in hepatocytes, adipocytes, and skeletal muscle cells, by causing abnormal cytokine expression/secretion from each cell. Adipose tissues, skeletal muscle, and the liver are the main endocrine organs producing hepatokines, adipokines, and myokines, respectively. In this review, we focus on the effect of IH on hepatokine, adipokine, and myokine expression. Full article

(This article belongs to the Special Issue Sleep Apnea and Intermittent Hypoxia 2.0)

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11 pages, 926 KiB

Open AccessReview

Obstructive Sleep Apnea as an Acceleration Trigger of Cellular Senescence Processes through Telomere Shortening

by Szymon Turkiewicz, Marta Ditmer, Marcin Sochal, Piotr Białasiewicz, Dominik Strzelecki and Agata Gabryelska

Int. J. Mol. Sci. 2021, 22(22), 12536; https://doi.org/10.3390/ijms222212536 - 21 Nov 2021

Cited by 23 | Viewed by 2902

Abstract

Obstructive sleep apnea (OSA) is chronic disorder which is characterized by recurrent pauses of breathing during sleep which leads to hypoxia and its two main pathological sequelae: oxidative stress and chronic inflammation. Both are also associated with cellular senescence. As OSA patients present [...] Read more.

Obstructive sleep apnea (OSA) is chronic disorder which is characterized by recurrent pauses of breathing during sleep which leads to hypoxia and its two main pathological sequelae: oxidative stress and chronic inflammation. Both are also associated with cellular senescence. As OSA patients present with higher prevalence of age-related disorders, such as atrial hypertension or diabetes mellitus type 2, a relationship between OSA and accelerated aging is observable. Furthermore, it has been established that these OSA are associated with telomere shortening. This process in OSA is likely caused by increased oxidative DNA damage due to increased reactive oxygen species levels, DNA repair disruptions, hypoxia, chronic inflammation, and circadian clock disturbances. The aim of the review is to summarize study outcomes on changes in leukocyte telomere length (LTL) in OSA patients and describe possible molecular mechanisms which connect cellular senescence and the pathophysiology of OSA. The majority of OSA patients are characterized by LTL attrition due to oxidative stress, hypoxia and inflammation, which make a kind of positive feedback loop, and circadian clock disturbance. Full article

(This article belongs to the Special Issue Sleep Apnea and Intermittent Hypoxia 2.0)

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19 pages, 1825 KiB

Open AccessReview

Cardiovascular Disorders Triggered by Obstructive Sleep Apnea—A Focus on Endothelium and Blood Components

by Jakub Mochol, Jakub Gawrys, Damian Gajecki, Ewa Szahidewicz-Krupska, Helena Martynowicz and Adrian Doroszko

Int. J. Mol. Sci. 2021, 22(10), 5139; https://doi.org/10.3390/ijms22105139 - 12 May 2021

Cited by 19 | Viewed by 3497

Abstract

Obstructive sleep apnea (OSA) is known to be an independent cardiovascular risk factor. Among arousal from sleep, increased thoracic pressure and enhanced sympathetic activation, intermittent hypoxia is now considered as one of the most important pathophysiological mechanisms contributing to the development of endothelial [...] Read more.

Obstructive sleep apnea (OSA) is known to be an independent cardiovascular risk factor. Among arousal from sleep, increased thoracic pressure and enhanced sympathetic activation, intermittent hypoxia is now considered as one of the most important pathophysiological mechanisms contributing to the development of endothelial dysfunction. Nevertheless, not much is known about blood components, which justifies the current review. This review focuses on molecular mechanisms triggered by sleep apnea. The recurrent periods of hypoxemia followed by reoxygenation promote reactive oxygen species (ROS) overproduction and increase inflammatory response. In this review paper we also intend to summarize the effect of treatment with continuous positive airway pressure (CPAP) on changes in the profile of the endothelial function and its subsequent potential clinical advantage in lowering cardiovascular risk in other comorbidities such as diabetes, atherosclerosis, hypertension, atrial fibrillation. Moreover, this paper is aimed at explaining how the presence of OSA may affect platelet function and exert effects on rheological activity of erythrocytes, which could also be the key to explaining an increased risk of stroke. Full article

(This article belongs to the Special Issue Sleep Apnea and Intermittent Hypoxia 2.0)

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14 pages, 1209 KiB

Open AccessReview

The Effect of Continuous Positive Airway Pressure Therapy on Obstructive Sleep Apnea-Related Hypertension

by Ronni Baran, Daniela Grimm, Manfred Infanger and Markus Wehland

Int. J. Mol. Sci. 2021, 22(5), 2300; https://doi.org/10.3390/ijms22052300 - 25 Feb 2021

Cited by 9 | Viewed by 5044

Abstract

Obstructive sleep apnea (OSA) is a common disease, with approximately 3–7% of men and 2–5% of women worldwide suffering from symptomatic OSA. If OSA is left untreated, hypoxia, microarousals and increased chemoreceptor stimulation can lead to complications like hypertension (HT). Continuous positive airway [...] Read more.

Obstructive sleep apnea (OSA) is a common disease, with approximately 3–7% of men and 2–5% of women worldwide suffering from symptomatic OSA. If OSA is left untreated, hypoxia, microarousals and increased chemoreceptor stimulation can lead to complications like hypertension (HT). Continuous positive airway pressure (CPAP) is the most common treatment for OSA, and it works by generating airway patency, which will counteract the apnea or hypopnea. More than one billion people in the world suffer from HT, and the usual treatment is pharmacological with antihypertensive medication (AHM). The focus of this review will be to investigate whether the CPAP therapy for OSA affects HT. Full article

(This article belongs to the Special Issue Sleep Apnea and Intermittent Hypoxia 2.0)

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