Obstructive sleep apnea and cognitive dysfunction

Felmet, Kelly A.; Petersen, Martha

doi:10.1097/01720610-200611000-00004

Cited by 11 publications

(7 citation statements)

References 29 publications

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“…It can lead to intermittent hypoxia (IH), sleep fragmentation and daytime sleepiness. OSA affects at least 4–10% of adults and has been reported as a critical predisposing factor for cardiovascular morbidity [ 1 – 4 ], metabolic disorder [ 5 , 6 ], hypertension and cognitive dysfunction [ 7 , 8 ]. Currently, several epidemiological studies have demonstrated that cancer progression and cancer-related mortality are accelerated in patients with OSA [ 9 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

Intermittent hypoxia promotes melanoma lung metastasis via oxidative stress and inflammation responses in a mouse model of obstructive sleep apnea

Ren

et al. 2018

Respir Res

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BackgroundRecently, increased tumor incidence and cancer-related mortality have been reported among patients with obstructive sleep apnea (OSA). Intermittent hypoxia (IH), the hallmark feature of OSA, contributes to the metastasis of tumors. However, the molecular mechanisms by which tumor metastasis is accelerated by OSA-like IH remain to be elucidated.MethodsC57BL/6 J male mice were subjected to intravenous injection of B16F10 melanoma cells before receiving IH treatment. Then, the animals were randomly distributed into three groups (n = 8 each): normoxia (N) group, IH group, and antioxidant tempol group (IHT, exposed to IH after treatment with tempol). After the mice were sacrificed, the number and weight of lung metastatic colonies were assessed. The lung tissues with tumor metastasis were analyzed for markers of oxidative stress and inflammation and for HIF-1α using western blotting and real-time PCR (qRT-PCR). The level of reactive oxygen species (ROS) in B16F10 cell was also assessed after N, IH and IH with tempol treatments.ResultsCompared with normoxia, IH significantly increased the number and weight of mouse lung metastatic colonies. Treatment of B16F10 cells with IH significantly enhanced ROS generation. Lung tissues with tumor metastasis provided evidence of increased oxidative stress, as assessed by p22phox and SOD mRNA levels and the NRF2 protein level, as well as increased inflammation, as assessed by TNF-α and IL-6 mRNA levels and the NF-κB P65 protein level. HIF-1α protein levels were increased in response to IH treatment. Tempol, an important antioxidant, ameliorated IH-induced melanoma lung metastasis in mice and reduced oxidative stress and inflammation responses.ConclusionsThese results support the hypothesis that oxidative stress and inflammation responses play an important role in the pathogenesis of OSA-like IH-induced melanoma lung metastasis in mice. Antioxidant intervention provides a novel strategy for the prevention and treatment of cancer in OSA populations.

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Section: Introductionmentioning

confidence: 99%

Intermittent hypoxia promotes melanoma lung metastasis via oxidative stress and inflammation responses in a mouse model of obstructive sleep apnea

Ren

et al. 2018

Respir Res

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“…Obstructive sleep apnea (OSA) is a prevalent condition characterized by repetitive occlusions of the upper airway during sleep resulting in intermittent hypoxia (IH), increased respiratory efforts and sleep fragmentation 1 . Over the last several decades, epidemiological, clinical and experimental evidences have provided significant support to the contention that OSA, and more specifically IH, operates as an independent risk factor for cardiovascular, cognitive and metabolic morbidities 2 3 4 . More recently, a potential link between OSA and cancer incidence and mortality has also been proposed based on epidemiological and animal studies 5 6 7 8 9 .…”

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confidence: 99%

Role of Cyclooxygenase-2 on Intermittent Hypoxia-Induced Lung Tumor Malignancy in a Mouse Model of Sleep Apnea

Campillo

Torres

Vilaseca

et al. 2017

Sci Rep

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An adverse role for obstructive sleep apnea (OSA) in cancer epidemiology and outcomes has recently emerged from clinical and animal studies. In animals, intermittent hypoxia (IH) mimicking OSA promotes tumor malignancy both directly and via host immune alterations. We hypothesized that IH could potentiate cancer aggressiveness through activation of the cyclooxygenase-2 (COX-2) pathway and the concomitant increases in prostaglandin E2 (PGE2). The contribution of the COX-2 in IH-induced enhanced tumor malignancy was assessed using celecoxib as a COX-2 specific inhibitor in a murine model of OSA bearing Lewis lung carcinoma (LLC1) tumors. Exposures to IH accelerated tumor progression with a tumor associated macrophages (TAMs) shift towards a pro-tumoral M2 phenotype. Treatment with celecoxib prevented IH-induced adverse tumor outcomes by inhibiting IH-induced M2 polarization of TAMs. Furthermore, TAMs isolated from IH-exposed mice treated with celecoxib reduced the proliferation of LLC1 naïve cells, while the opposite occurred with placebo-treated IH-exposed mice. Finally, in vitro IH exposures of murine macrophages and LLC1 cells showed that both cell types increased PGE2 release in response to IH. These results suggest a crucial role for the COX-2 signaling pathway in the IH-exacerbated malignant processes, and designate macrophages and lung adenocarcinoma cells, as potential sources of PGE2.

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“…OSA is associated with high rates of morbidity and mortality. It is a risk factor for cerebrovascular (12,132), cardiovascular (40,65,78,113,141), and metabolic diseases (52,87,109) as well as diabetes (10,73,100,122) and cognitive dysfunction (49,50). In recent years, OSA has been found to be associated with higher rates of cancer and increased cancer mortality (19, 25, 27-29, 90, 92, 105, 168).…”

mentioning

confidence: 99%

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

Hunyor

Cook

2018

American Journal of Physiology-Regulatory, Integrative and Comp

109

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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.

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Obstructive sleep apnea and cognitive dysfunction

Cited by 11 publications

References 29 publications

Intermittent hypoxia promotes melanoma lung metastasis via oxidative stress and inflammation responses in a mouse model of obstructive sleep apnea

Intermittent hypoxia promotes melanoma lung metastasis via oxidative stress and inflammation responses in a mouse model of obstructive sleep apnea

Role of Cyclooxygenase-2 on Intermittent Hypoxia-Induced Lung Tumor Malignancy in a Mouse Model of Sleep Apnea

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

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