scholarly journals Prolyl 4-Hydroxylase Domain Protein 3-Inhibited Smooth-Muscle-Cell Dedifferentiation Improves Cardiac Perivascular Fibrosis Induced by Obstructive Sleep Apnea

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Jiayi Tong ◽  
Fu-chao Yu ◽  
Yang Li ◽  
Qin Wei ◽  
Chen Li ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Smooth Muscle ◽  
Sleep Apnea ◽  
Therapeutic Potential ◽  
Obstructive Sleep ◽  
Domain Protein ◽  
Cardiovascular Fibrosis

Background. Intermittent hypoxia (IH) induced by obstructive sleep apnea (OSA) is a leading factor affecting cardiovascular fibrosis. Under IH condition, smooth muscle cells (SMAs) respond by dedifferentiation, which is associated with vascular remodelling. The expression of prolyl 4-hydroxylase domain protein 3 (PHD3) increases under hypoxia. However, the role of PHD3 in OSA-induced SMA dedifferentiation and cardiovascular fibrosis remains uncertain. Methods. We explored the mechanism of cardiovascular remodelling in C57BL/6 mice exposed to IH for 3 months and investigated the mechanism of PHD3 in improving the remodelling in vivo and vitro. Results. In vivo remodelling showed that IH induced cardiovascular fibrosis via SMC dedifferentiation and that fibrosis improved when PHD3 was overexpressed. In vitro remodelling showed that IH induced SMA dedifferentiation, which secretes much collagen I. PHD3 overexpression in cultured SMCs reversed the dedifferentiation by degrading and inactivating HIF-1α. Conclusion. OSA-induced cardiovascular fibrosis was associated with SMC dedifferentiation, and PHD3 overexpression may benefit its prevention by reversing the dedifferentiation. Therefore, PHD3 overexpression has therapeutic potential in disease treatment.

scholarly journals Modulation of TASK-1/3 channels at the hypoglossal motoneuron pool and effects on tongue motor output and responses to excitatory inputs in vivo: implications for strategies for obstructive sleep apnea pharmacotherapy

SLEEP ◽  
2020 ◽  
Author(s):  
Patrick Gurges ◽  
Hattie Liu ◽  
Richard L Horner
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Motor Activity ◽  
Cholinergic Neurons ◽  
Motor Nucleus ◽  
Channel Inhibition ◽  
Obstructive Sleep ◽  
Task Channel

Abstract Obstructive sleep apnea (OSA) occurs exclusively during sleep due to reduced tongue motor activity. Withdrawal of excitatory inputs to the hypoglossal motor nucleus (HMN) from wake to sleep contributes to this reduced activity. Several awake–active neurotransmitters with inputs to the HMN (e.g. serotonin [5-HT]) inhibit K+ leak mediated by TASK-1/3 channels on hypoglossal motoneurons, leading to increased neuronal activity in vitro. We hypothesize that TASK channel inhibition at the HMN will increase tongue muscle activity in vivo and modulate responses to 5-HT. We first microperfused the HMN of anesthetized rats with TASK channel inhibitors: doxapram (75 μM, n = 9), A1899 (25 μM, n = 9), ML365 (25 μM, n = 9), acidified artificial cerebrospinal fluid (ACSF, pH = 6.25, n = 9); and a TASK channel activator terbinafine (50 μM, n = 9); all with and without co-applied 5-HT (10 mM). 5-HT alone at the HMN increased tongue motor activity (202.8% ± 45.9%, p < 0.001). However, neither the TASK channel inhibitors, nor activator, at the HMN changed baseline tongue activity (p > 0.716) or responses to 5-HT (p > 0.127). Tonic tongue motor responses to 5-HT at the HMN were also not different (p > 0.05) between ChAT-Cre:TASKf/f mice (n = 8) lacking TASK-1/3 channels on cholinergic neurons versus controls (n = 10). In freely behaving rats (n = 9), microperfusion of A1899 into the HMN increased within-breath phasic tongue motor activity in wakefulness only (p = 0.005) but not sleep, with no effects on tonic activity across all sleep–wake states. Together, the findings suggest robust maintenance of tongue motor activity despite various strategies for TASK channel manipulation targeting the HMN in vivo, and thus currently do not support this target and direction for potential OSA pharmacotherapy.

scholarly journals Understanding the role of oxidative stress in the incidence of metabolic syndrome and obstructive sleep apnea

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Behnam Kargar ◽  
Zahra Zamanian ◽  
Majid Bagheri Hosseinabadi ◽  
Vahid Gharibi ◽  
Mohammad Sanyar Moradi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Obstructive Sleep Apnea ◽  
Logistic Regression ◽  
Sleep Apnea ◽  
International Diabetes Federation ◽  
Binary Logistic Regression ◽  
Stress Index ◽  
Obstructive Sleep

Abstract Background Understanding the causes and risk factors of metabolic syndrome is important for promoting population health. Oxidative stress has been associated with metabolic syndrome, and also obstructive sleep apnea. These are two diseases which have common prognostic characteristics for heart disease. The aim of this study was to examine the role of oxidative stress in the concurrent presence of metabolic syndrome and obstructive sleep apnea in a working population. Methods Participants were 163 artisan bakers in Shahroud, Iran, routinely exposed to significant heat stress and other oxidative stress indicators on a daily basis as part of their work. Using a cross-sectional design, data relevant to determining metabolic syndrome status according to International Diabetes Federation criteria, and the presence of obstructive sleep apnea according to the STOP-Bang score, was collected. Analyses included hierarchical binary logistic regression to yield predictors of the two diseases. Results Hierarchical binary logistic regression showed that oxidative stress – alongside obesity, no regular exercise, and smoking – was an independent predictor of metabolic syndrome, but not obstructive sleep apnea. Participants who were obese were 28 times more likely to have metabolic syndrome (OR 28.59, 95% CI 4.91–63.02) and 44 times more likely to have obstructive sleep apnea (OR 44.48, 95% CI 4.91–403.28). Participants meeting metabolic syndrome criteria had significantly higher levels of malondialdehyde (p <  0.05) than those who did not. No difference in oxidative stress index levels were found according to obstructive sleep apnea status. Conclusions Our findings suggest that oxidative stress contributes to the onset of metabolic syndrome, and that obstructive sleep apnea is involved in oxidative stress. Whilst obesity, exercise, and smoking remain important targets for reducing the incidence of metabolic syndrome and obstructive sleep apnea, policies to control risks of prolonged exposure to oxidative stress are also relevant in occupations where such environmental conditions exist.

scholarly journals Obstructive sleep apnea syndrome in non-obese patients

2021 ◽  
Author(s):  
Caterina Antonaglia ◽  
Giovanna Passuti
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Obstructive Sleep Apnea Syndrome ◽  
Sleep Apnea Syndrome ◽  
Obese Patients ◽  
Obstructive Sleep ◽  
Obese Subjects ◽  
Apnea Syndrome ◽  
Symptoms And Signs

AbstractObstructive sleep apnea syndrome (OSAS) is characterized by symptoms and signs of more than 5 apneas per hour (AHI) at polysomnography or 15 or more apneas per hour without symptoms. In this review, the focus will be a subgroup of patients: adult non-obese subjects with OSA and their specific features. In non-obese OSA patients (patients with BMI < 30 kg/m2), there are specific polysomnographic features which reflect specific pathophysiological traits. Previous authors identified an anatomical factor (cranial anatomical factors, retrognatia, etc.) in OSA non-obese. We have hypothesized that in this subgroup of patients, there could be a non-anatomical pathological prevalent trait. Little evidence exists regarding the role of low arousal threshold. This factor could explain the difficulty in treating OSA in non-obese patients and emphasizes the importance of a specific therapeutic approach for each patient.

scholarly journals Periodic limb movements in patients with obstructive sleep apnea syndrome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaobo Zhou ◽  
Bo Zhou ◽  
Zhe Li ◽  
Qiao Lu ◽  
Shaoping Li ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Obstructive Sleep Apnea Syndrome ◽  
Sleep Apnea Syndrome ◽  
Periodic Limb Movements ◽  
Limb Movements ◽  
Factors Associated ◽  
Obstructive Sleep ◽  
Apnea Syndrome

AbstractThe aim of the study was to assess the factors associated with periodic limb movements during sleep (PLMS) among obstructive sleep apnea syndrome (OSAS) patients and identify the role of PLMS in patients with OSAS. 303 adult patients with OSAS were included in the study. All patients completed physical examination, Epworth sleepiness scale (ESS), and polysomnography. Diagnosis of PLMS was made if the periodic leg movements index (PLMI) was ≥ 15. Chi-square test, ANOVA, univariate and multivariate logistic regression analyses were conducted to identify factors associated with PLMS among OSAS patients. Statistical analyses were performed with SPSS 26.0 for mac. Statistically significant difference was considered if P value < 0 .05. Among the 303 adult patients with OSAS, 98 patients had significant PLMS and the other 205 had no significant PLMS. Compared with OSAS patients without PLMS, OSAS patient with PLMS were older, had shorter REM duration and greater apnea–hypopnea index (AHI) (P < 0.05). The study suggests that PLMS is a matter of concern among patients with OSAS. A better understanding of the role of PLMS among OSAS patients could be useful in better recognition, intervention and treatment of OSAS.

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