Effects of intermittent hypoxia and hyperlipidemia-in vivo and in vitro studies on pathogenetic mechanisms linking obstructive sleep apnea to cardiovascular disease

2011 ◽  
Author(s):  
Qian Han
Keyword(s):  
Cardiovascular Disease ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
In Vitro Studies ◽  
Pathogenetic Mechanisms ◽  
Obstructive Sleep

scholarly journals Models of intermittent hypoxia and obstructive sleep apnea: molecular pathways and their contribution to cancer

2018 ◽  
Vol 315 (4) ◽  
pp. R669-R687 ◽  
Author(s):  
Imre Hunyor ◽  
Kristina M. Cook
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Inflammatory Responses ◽  
Hypoxia Inducible Factor ◽  
Small Animal ◽  
Molecular Pathways ◽  
Significant Heterogeneity ◽  
Obstructive Sleep

Obstructive sleep apnea (OSA) is common and linked to a variety of poor health outcomes. A key modulator of this disease is nocturnal intermittent hypoxia. There is striking epidemiological evidence that patients with OSA have higher rates of cancer and cancer mortality. Small-animal models demonstrate an important role for systemic intermittent hypoxia in tumor growth and metastasis, yet the underlying mechanisms are poorly understood. Emerging data indicate that intermittent hypoxia activates the hypoxic response and inflammatory pathways in a manner distinct from chronic hypoxia. However, there is significant heterogeneity in published methods for modeling hypoxic conditions, which are often lacking in physiological relevance. This is particularly important for studying key transcriptional mediators of the hypoxic and inflammatory responses such as hypoxia-inducible factor (HIF) and NF-κB. The relationship between HIF, the molecular clock, and circadian rhythm may also contribute to cancer risk in OSA. Building accurate in vitro models of intermittent hypoxia reflective of OSA is challenging but necessary to better elucidate underlying molecular pathways.

scholarly journals Obstructive Sleep Apnea and Circulating Biomarkers of Oxidative Stress: A Cross-Sectional Study

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 476
Author(s):  
Bernardo U. Peres ◽  
AJ Hirsch Allen ◽  
Aditi Shah ◽  
Nurit Fox ◽  
Ismail Laher ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Smoking History ◽  
Obstructive Sleep ◽  
History Of ◽  
Statin Usage ◽  
The Impact

Oxidative stress (OS) drives cardiometabolic diseases. Intermittent hypoxia consistently increases oxidative stress markers. Obstructive sleep apnea (OSA) patients experience intermittent hypoxia and an increased rate of cardiovascular disease, however, the impact of OSA on OS markers is not clear. The objective was to assess relationships between OSA severity and biomarker levels. Patients with suspected OSA referred for a polysomnogram (PSG) provided fasting blood sample. Plasma levels of 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), and superoxide dismutase (SOD) were measured. The relationship between OSA and OS was assessed both before and after controlling for confounders (age, sex, smoking history, history of cardiovascular disease, ethnicity, diabetes, statin usage, body mass index (BMI)). 402 patients were studied (68% male, mean age ± SD = 50.8 ± 11.8 years, apnea-hypopnea index (AHI) = 22.2 ± 21.6 events/hour, BMI = 31.62 ± 6.49 kg/m2). In a multivariable regression, the AHI significantly predicted 8-isoprostane levels (p = 0.0008) together with age and statin usage; AHI was not a predictor of 8-OHdG or SOD. Female sex (p < 0.0001) and no previous history of cardiovascular disease (p = 0.002) were associated with increased antioxidant capacity. Circulating 8-isoprostane levels may be a promising biomarker of the severity of oxidative stress in OSA patients. Prospective studies are needed to determine whether this biomarker is associated with long-term cardiometabolic complications in OSA.

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 &lt; 0.001). However, neither the TASK channel inhibitors, nor activator, at the HMN changed baseline tongue activity (p &gt; 0.716) or responses to 5-HT (p &gt; 0.127). Tonic tongue motor responses to 5-HT at the HMN were also not different (p &gt; 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.

The Impact of Chronic Intermittent Hypoxia on Cardiac Performance of Patients With Obstructive Sleep Apnea and Cardiovascular Disease

CHEST Journal ◽  
2015 ◽  
Vol 148 (4) ◽  
pp. 1058A
Author(s):  
Faisal Siddiqui ◽  
Madalina Macrea ◽  
Mitchell Horowitz ◽  
Thomas Martin ◽  
Tomer Pelleg ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Cardiac Performance ◽  
Chronic Intermittent Hypoxia ◽  
Obstructive Sleep ◽  
The Impact
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