Epigenetics: A Potential Mechanism Involved in the Pathogenesis of Various Adverse Consequences of Obstructive Sleep Apnea

Chen, Yung‐Che; Hsu, Po‐Yuan; Hsiao, Chang‐Chun

doi:10.3390/ijms20122937

Cited by 30 publications

(25 citation statements)

References 93 publications

(102 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consequently, the patient generally presents fatigue, excessive daytime sleepiness, morning headache, attention or memory impairment, and habitual snoring history, and carries increased risks of hypertension, ischemic heart disease, diabetes mellitus, and cognitive dysfunction. Recent randomized controlled trials have not demonstrated significant protective effects of long-term continuous positive airway pressure treatment on cardiovascular events or mortality, indicating the need of developing pharmaceutical agents to improve outcomes in OSA patients [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

Chen

Hsu

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

The purpose of this study is to explore the anti-inflammatory role of microRNAs (miR)-21 and miR-23 targeting the TLR/TNF-α pathway in response to chronic intermittent hypoxia with re-oxygenation (IHR) injury in patients with obstructive sleep apnea (OSA). Gene expression levels of the miR-21/23a, and their predicted target genes were assessed in peripheral blood mononuclear cells from 40 treatment-naive severe OSA patients, and 20 matched subjects with primary snoring (PS). Human monocytic THP-1 cell lines were induced to undergo apoptosis under IHR exposures, and transfected with miR-21-5p mimic. Both miR-21-5p and miR-23-3p gene expressions were decreased in OSA patients as compared with that in PS subjects, while TNF-α gene expression was increased. Both miR-21-5p and miR-23-3p gene expressions were negatively correlated with apnea hypopnea index and oxygen desaturation index, while TNF-α gene expression positively correlated with apnea hypopnea index. In vitro IHR treatment resulted in decreased miR-21-5p and miR-23-3p expressions. Apoptosis, cytotoxicity, and gene expressions of their predicted target genes-including TNF-α, ELF2, NFAT5, HIF-2α, IL6, IL6R, EDNRB, and TLR4-were all increased in response to IHR, while all were reversed with miR-21-5p mimic transfection under IHR condition. The findings provide biological insight into mechanisms by which IHR-suppressed miRs protect cell apoptosis via inhibit inflammation, and indicate that over-expression of the miR-21-5p may be a new therapy for OSA.

show abstract

Section: Introductionmentioning

confidence: 99%

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

Chen

Hsu

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Previous studies indicated a pivotal role of H3K4me3 and H3K9me3 over the promoter regions in epigenetic activation of the NOX-1, -2, -4, and -5 genes for cellular senescence and endothelial dysfunction [59,60]. Recently, it was suggested that sustained hypoxia can upregulate the oxygen-dependent demethylases (KDMs), which may increase demethylation of methylated lysine residues, including H3K9me3 and H3K4me3 [2,[61][62][63]. Another study showed histone modifications in oxidative stress pathways in aorta macrophages in mice exposed to IH [64].…”

Section: Osahs and Histone Modificationsmentioning

confidence: 99%

Obstructive Sleep Apnea-hypopnea Syndrome as a Novel Potential Risk for Aging

Li¹,

Wang²

2021

Aging and disease

View full text Add to dashboard Cite

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common sleep disorder, negatively influencing individuals' quality of life and socioeconomic burden. In recent years, OSAHS has been reported in not only constituting an aging-associated disease, but also in accelerating and/or potentiating aging mechanisms. However, the negative impacts of OSAHS on aging are underestimated because of low level of public awareness about this disease and high rates of undiagnosed cases, which are more critical in developing countries or economically disadvantaged regions. Hence, reviewing previously reported observations may assist scholars to better indicate that OSAHS is likely a novel potential risk for aging. Further understanding of the pathophysiological mechanism of OSAHS and its role in procession of aging may markedly highlight the importance of this common sleep disorder.

show abstract

“…The epigenetic modification mechanisms mainly include DNA methylation, histone tail modification, and non-coding RNA regulation, all of which modulate gene expression without changing the DNA sequence [20][21][22]. DNA hypermethylation is generally associated with gene silencing [23,24].…”

Section: Introductionmentioning

confidence: 99%

The Synergism of PGN, LTA and LPS in Inducing Transcriptome Changes, Inflammatory Responses and a Decrease in Lactation as Well as the Associated Epigenetic Mechanisms in Bovine Mammary Epithelial Cells

Sun

Dong

et al. 2020

Toxins

View full text Add to dashboard Cite

Mastitis is usually caused by a variety of pathogenic bacteria that include both Gram-positive and Gram-negative bacteria. Lipopolysaccharide (LPS) is the pathogen-associated molecular pattern (PAMP) of Gram-negative bacteria, and peptidoglycan (PGN) and lipoteichoic acid (LTA) are those of Gram-positive bacteria. The effects of LPS, PGN and/or LTA on inflammatory response and lactation in bovine mammary epithelial cells (BMECs) are well studied, but the epigenetic mechanisms of their effects received less attention. Furthermore, since the three PAMPs are often simultaneously present in the udder of cows with mastitis, it has implications in practice to study their additive effects. The results show that co-stimulation of bovine mammary epithelial cells with PGN, LTA, and LPS induced a higher number of differentially expressed genes (DEGs) and greater expressions of inflammatory factors including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α), chemokine (C-X-C motif) ligand (CXCL)1, and CXCL6. In addition, co-stimulation further increased DNA hypomethylation compared with sole LPS stimulation. Co-stimulation greatly decreased casein expression but did not further decrease histone acetylation levels and affect the activity of histone acetyltransferase (HAT) and histone deacetylase (HDAC), compared with sole LPS stimulation. Collectively, this study demonstrated that PGN, LTA, and LPS had an additive effect on inducing transcriptome changes and inflammatory responses in BMECs, probably through inducing a greater decrease in DNA methylation. Co-stimulation with PGN, LTA, and LPS decreased casein expression to a greater degree, but it might not be linked to histone acetylation and HAT and HDAC activity.

show abstract

Epigenetics: A Potential Mechanism Involved in the Pathogenesis of Various Adverse Consequences of Obstructive Sleep Apnea

Cited by 30 publications

References 93 publications

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

Obstructive Sleep Apnea-hypopnea Syndrome as a Novel Potential Risk for Aging

The Synergism of PGN, LTA and LPS in Inducing Transcriptome Changes, Inflammatory Responses and a Decrease in Lactation as Well as the Associated Epigenetic Mechanisms in Bovine Mammary Epithelial Cells

Contact Info

Product

Resources

About