An Insight into the Changes in Human Plasma Proteome on Adaptation to Hypobaric Hypoxia

Ahmad, Yasmin; Sharma, Narendra Kumar; Garg, Iti; Ahmad, Mohammad Faiz; Sharma, Manish; Bhargava, Kalpana

doi:10.1371/journal.pone.0067548

Cited by 51 publications

(48 citation statements)

References 93 publications

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“…Furthermore, the association found between lowest SaO 2 and serum vitamin D levels could suggest that hypoxia is a putative factor involved in vitamin D deficiency in patients with OSA, as reported in chronic obstructive pulmonary diseases. 23 However, considering that vitamin D binding-protein (VDBP) changes its serum level in response to chronic hypoxia, 24 further investigation of VDBP serum levels in patients with OSA before and after CPAP treatment would be necessary in the future.…”

Section: Discussionmentioning

confidence: 99%

Continuous Positive Airway Pressure Treatment Increases Serum Vitamin D Levels in Male Patients with Obstructive Sleep Apnea

Liguori

Romigi

Izzi

et al. 2015

Journal of Clinical Sleep Medicine

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BRIEF SUMMARYCurrent Knowledge/Study Rationale: Vitamin D not only participates in bone metabolism and regulates calcium homeostasis, but also has pleiotropic effects, modulating numerous metabolic processes. Considering that patients with obstructive sleep apnea (OSA) suffer from vitamin D defi ciency and show high serum parathyroid hormone (PTH) levels, we tested the effects of short-term continuous positive airway pressure (CPAP) on serum vitamin D and PTH levels. Study Impact: These fi ndings suggest that short-term CPAP therapy in male patients with OSA determines an increase of serum vitamin D levels. Therefore, the current study provides evidence that OSA seems to be an etiopathogenetic factor involved in vitamin D defi ciency, which may recover after CPAP therapy in male patients. Study Objective:Recent studies report a link between obstructive sleep apnea (OSA) syndrome, low vitamin D levels, and high parathyroid hormone (PTH) concentrations. The aim of the current study is to evaluate the effect of 7-night continuous positive airway pressure (CPAP) therapy on serum vitamin D, PTH, and calcium levels in patients with severe OSA syndrome. Methods: Patients with severe OSA were enrolled into the study and compared to control subjects. Patients with OSA underwent CPAP therapy for 7 nights and were consequently divided into responders (OSA-R, mean residual AHI < 5/h) and nonresponders (OSA-nR, mean residual AHI > 5/h). Serum vitamin D, PTH, and calcium levels were measured at baseline in patients with severe OSA (apnea-hypopnea index > 30/h) and control subjects. Patients with OSA underwent a fi nal morning blood sample after 7-night CPAP therapy. Results: We enrolled 90 patients with OSA into the study (65 OSA-R and 25 OSA-nR) compared to 32 control subjects. At baseline, lower vitamin D and higher PTH levels were detected in the OSA group compared to controls. After 7-night CPAP therapy, male OSA-R patients showed a signifi cant increase in vitamin D levels. Conversely, female OSA-R patients did not show the same increase in vitamin D levels. It was also observed that OSA-nR subjects did not show modifi cations of serum markers after nCPAP-therapy. Conclusions:The study demonstrates that short-term nCPAP treatment is able to promote the recovery of vitamin D homeostasis in male patients with OSA. The mediation of sexual hormones in regulating vitamin D is a possible explanation of the lack of recovery of vitamin D homeostasis in female patients with OSA as it often affects postmenopausal women. Keywords: calcium, CPAP, OSA, PTH, vitamin D Citation: Liguori C, Romigi A, Izzi F, Mercuri NB, Cordella A, Tarquini E, Giambrone MP, Marciani MG, Placidi F. Continuous positive airway pressure treatment increases serum vitamin D levels in male patients with obstructive sleep apnea.

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Section: Discussionmentioning

confidence: 99%

Continuous Positive Airway Pressure Treatment Increases Serum Vitamin D Levels in Male Patients with Obstructive Sleep Apnea

Liguori

Romigi

Izzi

et al. 2015

Journal of Clinical Sleep Medicine

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“…The effect of LTH on PTH levels explains the synergistic interaction of LTH with pregnancy on increased levels of bioactive vitamin D. Finally, our study revealed that this ovine LTH model is unique in showing LTH decreases in renal CYP24a1. Previous in vitro studies have shown that hypoxia upregulates the expression of CYP27b1, CYP24a1, and VDBP gene expression in human cells (1,27). The effect of hypobaric hypoxia on VDR-related gene expression is thought to be indirect, as there are no consensus hypoxia-inducible factor-1␣ DNA-binding elements in these genes (8,19).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D status and metabolism in an ovine pregnancy model: effect of long-term, high-altitude hypoxia

Goyal

Billings²,

Mansour³

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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Vitamin D status increases during healthy mammalian pregnancy, but the molecular determinants remain uncharacterized. The first objective of this study was to determine the effects of pregnancy, and the second objective was to examine the role of chronic hypoxia on vitamin D status and metabolism in an ovine model. We analyzed the plasma levels of cholecalciferol, 25-OH-D, and 1␣,25-(OH)2D in nonpregnant ewes, near-term pregnant ewes, and their fetuses exposed to normoxia (low altitude) or hypoxia (high-altitude) for 100 days. Hypoxic sheep had increased circulating levels of 25-OH-D and 1␣,25-(OH)2D compared with normoxic sheep. Hypoxia increases in 25-OH-D were associated with increased expression of renal 25-hydroxylases CYP2R1 and CYP2J. Pregnancy did not increase further the plasma levels of 25-OH-D, but it significantly increased those of the active metabolite, 1␣,25-(OH)2D, in both normoxic and hypoxic ewes. Increased bioactivation of vitamin D correlated with increased expression of the vitamin D-activating enzyme CYP27b1 and decreased expression of the inactivating enzyme CYP24a1 in maternal kidneys and placentas. Hypoxia increased parathyroid hormone levels and further increased renal CYP27b1. Pregnancy and hypoxia decreased the expression of vitamin D receptor (VDR) in maternal kidney and lung, with opposite effects on placental VDR. We conclude that ovine pregnancy is a model of increased vitamin D status, and long-term hypoxia further improves vitamin D status due to pregnancy-and hypoxia-specific regulation of VDR and metabolic enzymes.pregnancy; hypoxia; vitamin D; metabolism; kidney; placenta VITAMIN D HAS WELL-ESTABLISHED CLASSIC EFFECTS on bone metabolism and mineral homeostasis (8,33). In addition, vitamin D has important noncalcemic roles in the reproductive, cardiovascular, renal, lung, immune, neuronal, and pancreatic systems (8, 33). In reproduction, vitamin D deficiency has been associated with sterility, placental insufficiency, intrauterine growth restriction, recurrent miscarriages, gestational diabetes, and preeclampsia (maternal high blood pressure and proteinuria) (6, 51-53). Furthermore, maternal vitamin D deficiency has been also linked to postnatal infectious diseases, autoimmune diseases (diabetes type I), asthma, and obesity (26,28,54).Vitamin D 3 (cholecalciferol) can be produced endogenously from 7-dehydrocholesterol by sun exposure in the skin epidermis or obtained from dietary sources (8,33 (14). A classic gene regulated in this manner is the vitamin D-inactivating enzyme CYP24A1 (24-hydroxylase). Most cells that express VDR also express CYP24A1, providing a unique negative feedback control mechanism to regulate the vitamin D effects (8,14). In healthy nonpregnant mammals, the circulating levels of 1␣,25-(OH) 2 D are tightly regulated; low levels of 1␣,25-(OH) 2 D stimulate the release of parathyroid hormone (PTH) that upregulates renal CYP27b1 expression, and high levels of 1␣,25-(OH) 2 D stimulates VDR that upregulates CYP24a1 expression (8, 33).The metabolism of vitamin ...

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“…Nonetheless, given that vitamin D binding protein (VDBP) changes its serum level in response to chronic hypoxia, further investigation is warranted to better understand this relationship [70]. …”

Section: Osas and Vitamin D Insufficiencymentioning

confidence: 99%

The role of vitamin D in obstructive sleep apnoea syndrome

Archontogeorgis

Nena

Παπάνας

et al. 2018

Breathe

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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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An Insight into the Changes in Human Plasma Proteome on Adaptation to Hypobaric Hypoxia

Cited by 51 publications

References 93 publications

Continuous Positive Airway Pressure Treatment Increases Serum Vitamin D Levels in Male Patients with Obstructive Sleep Apnea

Continuous Positive Airway Pressure Treatment Increases Serum Vitamin D Levels in Male Patients with Obstructive Sleep Apnea

Vitamin D status and metabolism in an ovine pregnancy model: effect of long-term, high-altitude hypoxia

The role of vitamin D in obstructive sleep apnoea syndrome

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