Search

Recent studies have evaluated the potential of circulating microRNAs (miRNAs) as valuable biomarkers for characterizing obstructive sleep apnea (OSA) in males. The potential use of miRNAs as clinical indicators in females is unknown. The objective is to identify a set of miRNAs to be used as endogenous controls (ECs) in female patients with OSA. Then, to analyze differences in the miRNA expression profile between patients with and without OSA. This observational, longitudinal study included 85 females with suspected OSA who underwent a polysomnography. OSA was defined as an apnea hypopnea index ≥ 15 events/h. The study population was stratified into 50 OSA patients and 38 non-OSA patients. Exploratory expression profiling of 188 miRNAs consistent and reliable in plasma was performed in a discovery cohort of 21 patients by TaqMan-Low-Density-Array (TLDA). The best ECs were identified by mean centre + standard deviation normalization and concordance correlation restricted normalization. Differentially expressed candidate miRNAs were selected for RT-qPCR validation in a validation cohort of 64 patients. Three circulating miRNAs (miR-30a-5p, miR-93-3p and miR-532-5p) were identified as most stable for use as ECs. Twenty-seven miRNA candidates were identified as potential biomarkers for OSA screening (p value < 0.025) in the TLDA cohort. However, validation cohort showed no differences in the circulating miRNA profile in female patients with and without OSA. We identified a set of ECs in females with OSA that may contribute to result homogeneity in determining circulating miRNAs. Exploratory analysis did not identify a significantly miRNA profile between female patients with and without OSA., (© 2022. The Author(s).)

Introduction: Obstructive sleep apnea (OSA) is a chronic, heterogeneous and multicomponent disorder with associated cardiovascular and metabolic alterations. Despite being the most common sleep-disordered breathing, it remains a significantly undiagnosed condition., Objective: We examined the plasma metabolome and lipidome of patients with suspected OSA, aiming to identify potential diagnosis biomarkers and to provide insights into the pathophysiological mechanisms underlying the disease. Additionally, we evaluated the impact of continuous positive airway pressure (CPAP) treatment on the circulating metabolomic and lipidomic profile., Material and Methods: Observational-prospective-longitudinal study including 206 consecutive subjects referred to the sleep unit. OSA was defined as an apnea-hypopnoea index ≥ 15 events/h after polysomnography (PSG). Patients treated with CPAP were followed-up for 6 months. Untargeted plasma metabolomic and lipidomic profiling was performed using liquid chromatography coulpled to massspectrometry., Results: A plasma profile composed of 33 metabolites (mainly glycerophospholipids and bile acids) was identified in OSA vs. non-OSA patients. This profile correlated with specific PSG measures of OSA severity related to sleep fragmentation and hypoxemia. Machine learning analyses disclosed a 4-metabolites-signature that provided an accuracy (95% CI) of 0.98 (0.95-0.99) for OSA detection. CPAP treatment was associated with changes in 5 plasma metabolites previously altered by OSA., Conclusions: This analysis of the circulating metabolome and lipidome reveals a molecular fingerprint of OSA, which was modulated after effective CPAP treatment. Our results suggest blood-based biomarker candidates with potential application in the personalized management of OSA and suggest the activation of adaptive mechanisms in response to OSA-derived hypoxia., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Rationale: Evidence suggests that the physiopathologic consequences of obstructive sleep apnea (OSA) resemble those induced by aging. Some studies report that the deleterious effects associated with OSA might be age dependent. Objectives: To evaluate the association of OSA with the aging process and to determine whether this association is maintained across different age groups. Methods: This was an observational, prospective study including 599 patients with suspected OSA. Five hallmarks of aging were evaluated: alteration of cellular communication (serum CRP [C-reactive protein] concentration), deregulation of nutrient sensing (insulin resistance), telomere attrition (leukocyte telomeric length), mitochondrial dysfunction (leukocyte mitochondrial DNA copy number), and genomic instability (urinary 8-hydroxy-2-deoxyguanosine concentration). For age-stratified analyses, subjects were divided into four groups according to the apnea-hypopnea index (AHI) and the median age (50 yr): young patients without OSA (age < 50 yr old, AHI < 15 events/h), young patients with OSA (age < 50 yr old, AHI ⩾ 15 events/h), older patients without OSA (age ⩾ 50 yr old, AHI < 15 events/h), and older patients with OSA (age ⩾ 50 yr old, AHI ⩾ 15 events/h). Results: A dose-response relationship was found between the AHI, arousal index, and time during the night spent with an oxygen saturation less than 90% and the following hallmarks: alteration of cellular communication, deregulation of nutrient sensing, mitochondrial dysfunction, and genomic instability. Considering age-stratified analyses, OSA was associated with an increase in several hallmarks of aging in young patients, but no significant association of OSA was identified in older patients. Conclusions: In subjects under 50 years of age, OSA is associated with an increase in specific hallmarks of aging, independent of several known confounding factors.

Background: Membrane-derived extracellular vesicles (EVs) are released to the circulation by cells found in adipose tissue, transferring microRNAs (miRNAs) that may mediate the adaptive response of recipient cells. This study investigated plasma EVs from obese vs. nonobese women and their functional impact in adipocytes., Methods: Plasma EVs were isolated by differential centrifugation. Concentration and size were examined by nanoparticle tracking analysis (NanoSight). RNA was purified from plasma and plasma EVs of 45 women (47 ± 12 years, 58% of obesity) and profiles of mature miRNAs were assessed. Functional analyses were performed in human adipocytes., Findings: Smaller plasma EVs were found in obese when compared to nonobese women. Positive associations were identified between circulating EVs numbers and parameters of impaired glucose tolerance. Almost 40% of plasma cell-free miRNAs were also found in isolated plasma EVs, defined as Ct values < 37 in ≥75% of samples. BMI together with parameters of insulin resistance were major contributors to EVs-contained miRNA patterns. Treatments of cultured human adipocytes with EVs from obese women led to a significant reduction of genes involved in lipid biosynthesis, while increasing the expression of IRS1 (12.3%, p = 0.002)., Interpretation: Size, concentration and the miRNA cargo of plasma EVs are associated with obesity and parameters of insulin resistance. Plasma EVs may mediate intercellular communication relevant to metabolism in adipocytes., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Obstructive sleep apnea (OSA) is a common disease caused by repeated episodes of collapse of the upper airway during sleep and is associated with the development of cardiovascular disease (CVD). However, there is high heterogeneity in the impact of OSA on patients. Until now, the profile of OSA patients at risk of developing CVD has not been defined, including the measurable variables that could be used to predict the CVD risk of a patient with OSA., Objective: The aim of this study was to identify the microRNA (mi-RNA) profile associated with CVD in patients with OSA., Method: This is an observational, cross-sectional study that included 132 male patients. Three groups were defined as OSA patients, OSA patients with hypertension, and OSA patients who developed a major cardiovascular event. Polysomnography and ambulatory blood pressure measurements were performed. The expression profiling of 188 miRNAs in plasma was performed in 21 subjects (matched by BMI and age) by the TaqMan low density array (TLDA). miRNAs differentially expressed in the different subgroups of patients and miRNAs that correlated with the cardiovascular risk SCORE were selected for validation by RT-qPCR in the 111 remaining patients., Results: From the TLDA analysis, 7 miRNAs were selected for validation. Differential expression was not confirmed in any of the miRNAs. miR-143 was associated with nocturnal systolic blood pressure. miR-107 correlated with 24-h blood pressure parameters and with nocturnal hypertension. miR-486 was associated with the cardiovascular risk SCORE., Conclusions: The circulating profile of miRNAs does not seem to be different in any of the subgroups of patients with OSA and different cardiovascular risk factors. Nevertheless, miR-107 and miR-143 are associated with specific blood pressure parameters in patients with OSA and miR-486 is associated with the cardiovascular risk SCORE., (© 2020 S. Karger AG, Basel.)

Evaluation of microRNAs (miRNAs) could allow characterization of the obstructive sleep apnea (OSA) and help diagnose it more accurately. We aimed to examine circulating miRNA profiles to establish the differences between non-OSA and OSA patients. Additionally, we aimed to analyse the effect of continuous positive airway pressure (CPAP) treatment on the miRNA profile. This observational, longitudinal study included 230 subjects referred to the Sleep Unit due to suspected OSA. Expression profiling of 188 miRNAs in plasma was performed in 27 subjects by TaqMan-Low-Density-Array. OSA-related miRNAs were selected for validation by RT-qPCR in 203 patients. Prediction models were built to discriminate between non-OSA and OSA: 1) NoSAS-score, 2) differentially expressed miRNAs, and 3) combination of NoSAS-score plus miRNAs. The differentially expressed miRNAs were measured after 6 months of follow-up. From the 14 miRNAs selected for validation, 6 were confirmed to be differentially expressed. The areas under the curve were 0.73 for the NoSAS-score, 0.81 for the miRNAs and 0.86 for the combination. After 6 months of CPAP treatment, miRNA levels in the OSA group seem to approximate to non-OSA levels. A cluster of miRNAs was identified to differentiate between non-OSA and OSA patients. CPAP treatment was associated with changes in the circulating miRNA profile.

Background: Continuous positive airway pressure (CPAP) treatment reduces blood pressure (BP) in obstructive sleep apnoea (OSA) and hypertensive patients, but there is a lack of data about the effects of CPAP on the BP in normotensive patients., Objective: The aim of the study was to evaluate BP changes in normotensive OSA individuals receiving CPAP treatment., Methods: We selected 131 normotensive outpatients with an apnoea/hypopnoea index (AHI) greater than 15 events/hour who required CPAP treatment. All patients underwent a sleep study and 24-h ambulatory BP monitoring (ABPM) at baseline and after 6 months. In addition, the patients were assessed for the presence of baseline masked hypertension, defined as office BP less than 140/90 mmHg and increased BP on 24-h ABPM (mean 24-h BP ≥130/80 mmHg)., Results: After 6 months of CPAP treatment, a mild reduction in all 24-h ABPM variables was observed, but only the mean 24-h DBP [-1.39 mmHg, 95% confidence interval (95% CI), -2.50 to -0.27], mean daytime DBP (-1.39 mmHg, 95% CI -2.56 to -0.22) and the mean 24-h ambulatory BP (-1.80 mmHg, 95% CI, -3.16 to -0.44) reached statistical significance. The reduction was primarily due to BP changes in individuals with masked hypertension who displayed a mean BP reduction of -4.78 mmHg (-7.25 to -2.30 mmHg). Consistent with a circadian BP pattern, a reduction in mean nocturnal BP of -4.73 mmHg (-7.39 to -2.06 mmHg) was observed at 6 months in nondippers; in contrast, the mean nocturnal BP in dippers increased by 2.61 mmHg (0.60-4.62 mmHg)., Conclusion: Our findings suggest that the CPAP effects may be different in normotensive outpatients depending on the presence of undiagnosed masked hypertension and the dipping pattern. Therefore, it is important to consider measuring ABPM in this type of patient.

microRNAs (miRNAs) are non-coding RNAs highly relevant as biomarkers for disease. A seminal study that explored the role of miRNAs in obstructive sleep apnea syndrome (OSA) demonstrated their usefulness in clinical management. Nevertheless, the miRNAs that may act as endogenous controls (ECs) have not yet been established. The identification of ECs would contribute to the standardization of these biomarkers in OSA. The objective of the study is to identify miRNAs that can be used as ECs in OSA. We evaluated 100 patients divided into two different cohorts: a learning cohort of 10 non-OSA and 30 OSA patients, and a validation cohort (20 non-OSA and 40 OSA patients). In the learning cohort, a profile of 188 miRNAs was determined in plasma by TaqMan Low Density Array. The best EC candidates were identified by mean center+SD normalization and concordance correlation restricted normalization. The results were validated using NormFinder and geNorm to assess the stability of those ECs. Eight miRNAs were identified as EC candidates. The combination miRNA-106a/miRNA-186 was identified as the most stable among all candidates. We identified a set of ECs to be used in the determination of circulating miRNA in OSA that may contribute to the homogeneity of results., Competing Interests: The authors have declared that no competing interests exist.

The goal of this study was to assess the relationship between the severity of obstructive sleep apnoea (OSA) and the levels of carcinogenesis- and tumour growth-related biomarkers in patients with cutaneous melanoma.This multicentre observational study included patients who were newly diagnosed with melanoma. The patients were classified as non-OSA (apnoea-hypopnoea index (AHI) 0-5 events·h -1 ), mild OSA (AHI 5-15 events·h -1 ) and moderate-severe OSA (AHI >15 events·h -1 ). ELISAs were performed to analyse the serum levels of hypoxia- and tumour adhesion-related biomarkers (vascular endothelial growth factor (VEGF), interleukin (IL)-8, intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)-1) and markers of tumour aggressiveness (S100 calcium-binding protein B (S100B) and melanoma inhibitory activity (MIA)). A logistic model adjusted for age, sex and body mass index was fitted to each biomarker, and the AHI served as the dependent variable.360 patients were included (52.2% male, median (interquartile range) age 55.5 (43.8-68.0) years and AHI 8.55 (2.8-19.5) events·h -1 ). The levels of VEGF, IL-8, ICAM-1, S100B and MIA were not related to the severity of OSA. The levels of VCAM-1 were higher in patients with OSA than those without OSA (mild OSA: odds ratio (OR) 2.07, p=0.021; moderate-severe OSA: OR 2.35, p=0.013).In patients with cutaneous melanoma, OSA was associated with elevated circulating levels of VCAM-1 that could indicate the contribution of OSA in tumorigenesis via integrin-based adhesion., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2018.)