Serum Levels of Vascular Endothelial Growth Factor and Insulin-like Growth Factor Binding Protein-3 in Obstructive Sleep Apnea Patients: Effect of Continuous Positive Airway Pressure Treatment

Archontogeorgis, Kostas; Nena, Evangelia; Παπάνας, Νικόλαος; Xanthoudaki, Maria; Hatzizisi, Olga; Kyriazis, George A.; Tsara, Venetia; Maltezos, Efstratios; Froudarakis, Marios; Steiropoulos, Paschalis

doi:10.2174/1874192401509010133

Cited by 8 publications

(6 citation statements)

References 46 publications

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“…In the present study, we have demonstrated using our 3D in vitro model that an anti-VEGF is able to decrease tumor proliferation in terms of cell viability and tumor-spheroid size in two different tumor cell lines. These results are in line with other studies which largely demonstrate that VEGF serum levels are correlated with apnea hypopanea and oxygen desaturation indexes, besides the fact that VEGF levels decrease after 6 months on CPAP treatment, altogether indicating the association of the severity of the OSA pathology with VEGF serum levels [ 27 – 30 ].…”

Section: Discussionsupporting

confidence: 91%

Obstructive Sleep Apnea Monocytes Exhibit High Levels of Vascular Endothelial Growth Factor Secretion, Augmenting Tumor Progression

Cubillos‐Zapata

Hernández-Jiménez

Avendaño-Ortíz

et al. 2018

Mediators of Inflammation

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Obstructive sleep apnea (OSA) is a syndrome characterized by repeated pauses in breathing induced by a partial or complete collapse of the upper airways during sleep. Intermittent hypoxia (IH), a hallmark characteristic of OSA, has been proposed to be a major determinant of cancer development, and patients with OSA are at a higher risk of tumors. Both OSA and healthy monocytes have been found to show enhanced HIF1α expression under IH. Moreover, these cells under IH polarize toward a tumor-promoting phenotype in a HIF1α-dependent manner and influence tumor growth via vascular endothelial growth factor (VEGF). Monocytes from patients with OSA increased the tumor-induced microenvironment and exhibited an impaired cytotoxicity in a 3D tumor in vitro model as a result of the increased HIF1α secretion. Adequate oxygen restoration both in vivo (under continuous positive airway pressure treatment, CPAP) and in vitro leads the monocytes to revert the tumor-promoting phenotype, demonstrating the plasticity of the innate immune system and the oxygen recovery relevance in this context.

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Section: Discussionsupporting

confidence: 91%

Obstructive Sleep Apnea Monocytes Exhibit High Levels of Vascular Endothelial Growth Factor Secretion, Augmenting Tumor Progression

Cubillos‐Zapata

Hernández-Jiménez

Avendaño-Ortíz

et al. 2018

Mediators of Inflammation

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“…In another study in 38 T2DM patients, those who were compliant with CPAP were less likely to progress to advanced retinopathy [ 18 ]. As CPAP treatment was shown to downregulate renin-angiotensin-aldosterone activity [ 46 ] and reduce VEGF levels [ 47 ] in those without diabetes, these could possibly be mechanistic pathways by which CPAP use is associated with reduced risk of DKD and retinopathy. No data are available with regard to neuropathy.…”

Section: Discussionmentioning

confidence: 99%

The Relationship between Diabetes-Related Complications and Obstructive Sleep Apnea in Type 2 Diabetes

Siwasaranond

Nimitphong

Manodpitipong

et al. 2018

Journal of Diabetes Research

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This study explored the relationship between obstructive sleep apnea (OSA) and the presence of any diabetes-related complications in type 2 diabetes and whether this was mediated by hypertension. Secondly, the relationship between OSA severity and estimated glomerular filtration rate (eGFR) was investigated. A total of 131 patients participated. OSA was diagnosed using a home monitor, and severity was measured by apnea-hypopnea index (AHI) and oxygen desaturation index (ODI). OSA was found in 75.6% of the participants, 40.5% with moderate-to-severe degree. Any diabetes-related complications (retinopathy, neuropathy, nephropathy, or coronary artery disease) were present in 55.5%, and 70.2% of the participants had hypertension. Mediation analysis indicated that, compared to those with mild or no OSA, those with moderate-to-severe OSA were 3.05 times more likely to have any diabetes-related complications and that this relationship was mediated by the presence of hypertension. After adjusting for confounders, ODI (B = −0.036, p = 0.041), but not AHI, was significantly associated with lower eGFR. In conclusion, moderate-to-severe OSA was related to the presence of any diabetes-related complications in type 2 diabetes, and the relationship was mediated by hypertension. The severity of intermittent hypoxia was associated with lower eGFR. Whether OSA treatment will delay or reduce diabetes-related complications should be investigated.

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“…HIF-1α expression was downregulated after 2 months of CPAP therapy (1.10±0.21 before versus 0.78±0.32 ng⋅mL −1 after CPAP treatment, p<0.001) [65]. Similarly, in another study, VEGF serum levels were higher in OSAS patients compared with controls (398.4±229 versus 229.9±149.8 pg⋅mL −1 , respectively, p<0.001) [66]. VEGF levels were positively correlated with AHI (r=0.336, p=0.001) and ODI (r=0.282, p=0.007), while 6 months of CPAP therapy significantly decreased VEGF serum concentrations in OSAS patients (p<0.001) [66].…”

Section: Osas and Vitamin D Insufficiencymentioning

confidence: 99%

The role of vitamin D in obstructive sleep apnoea syndrome

Archontogeorgis

Nena

Παπάνας

et al. 2018

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Obstructive sleep apnoea syndrome (OSAS) is a common disorder of multifactorial pathogenesis and is associated with obesity, diabetes and cardiovascular disease. Vitamin D is a fat-soluble vitamin with an important function in calcium absorption and homeostasis, which is also implicated in several nonskeletal conditions. The prevalence of vitamin D deficiency is increasing worldwide and is associated with similar metabolic disturbances to OSAS. Moreover, recent data suggest that in OSAS patients serum levels of vitamin D are lower compared with non-apnoeic subjects. However, the mechanisms linking vitamin D deficiency and OSAS are not completely understood and several hypotheses have been advanced. To date, a limited number of studies have assessed the association between lower serum concentrations of vitamin D and OSAS, and have reported inconsistent results. Similarly, contradictory results have been produced by studies which evaluated the effect of continuous positive airway pressure treatment on serum vitamin D levels. The aim of this review is to summarise current knowledge on the association between OSAS and vitamin D levels.Key pointsVitamin D insufficiency prevalence is increasing worldwide and presents with similar comorbidities and risk factors to OSAS.The nonskeletal actions of vitamin D may contribute to the development of OSAS through immune system modulation, myopathy and inflammation.Studies evaluating serum vitamin D concentrations in OSAS patients and the effect of CPAP treatment report contradictory results, often influenced by confounding factors, such as obesity.There appears to be potential for use of vitamin D supplementation in OSAS patients as a means of reducing the incidence of cardiovascular disease, a comorbidity common in both conditions.Educational aimsTo assess the potential association between OSAS and serum levels of vitamin D.To discuss the pathogenetic mechanisms linking OSAS and vitamin D insufficiency.To illustrate the effect of CPAP treatment on vitamin D concentration in OSAS patients.

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Serum Levels of Vascular Endothelial Growth Factor and Insulin-like Growth Factor Binding Protein-3 in Obstructive Sleep Apnea Patients: Effect of Continuous Positive Airway Pressure Treatment

Cited by 8 publications

References 46 publications

Obstructive Sleep Apnea Monocytes Exhibit High Levels of Vascular Endothelial Growth Factor Secretion, Augmenting Tumor Progression

Obstructive Sleep Apnea Monocytes Exhibit High Levels of Vascular Endothelial Growth Factor Secretion, Augmenting Tumor Progression

The Relationship between Diabetes-Related Complications and Obstructive Sleep Apnea in Type 2 Diabetes

The role of vitamin D in obstructive sleep apnoea syndrome

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