Browsing by Author "Pinto, Paula"
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- Evening and morning alterations in Obstructive Sleep Apnea red blood cell proteomePublication . Feliciano, Amélia; Vaz, Fátima; Valentim-Coelho, Cristina; Torres, Vukosava M.; Silva, Rita; Prosinecki, Vesna; Alexandre, Bruno M.; Almeida, Andreia; Almeida-Marques, Catarina; Carvalho, Ana S.; Matthiesen, Rune; Malhotra, Atul; Pinto, Paula; Bárbara, Cristina; Penque, DeborahThis article presents proteomics data referenced in [1] Using proteomics-based evaluation of red blood cells (RBCs), we have identified differentially abundant proteins associated with Obstructive Sleep Apnea Syndrome (OSA). RBCs were collected from peripheral blood of patients with moderate/severe OSA or snoring at pre- (evening) and post-night (morning) polysomnography, so that proteome variations between these time points could be assessed. RBC cytoplasmic fraction depleted of hemoglobin, using Hemovoid(™) system, were analyzed by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), the 2D image software-based analyzed and relevant differentially abundant proteins identified by mass spectrometry (MS). MS identified 31 protein spots differentially abundant corresponding to 21 unique proteins possibly due to the existence of post-translational modification regulations. Functional analysis by bioinformatics tools indicated that most proteins are associated with catalytic, oxidoreductase, peroxidase, hydrolase, ATPase and anti-oxidant activity. At morning a larger numbers of differential proteins including response to chemical stimulus, oxidation reduction, regulation of catalytic activity and response to stress were observed in OSA. The data might support further research in OSA biomarker discovery and validation.
- Evening and morning peroxiredoxin-2 redox/oligomeric state changes in obstructive sleep apnea red blood cells: Correlation with polysomnographic and metabolic parametersPublication . Feliciano, Amélia; Vaz, Fátima; Torres, Vukosava M.; Valentim-Coelho, Cristina; Silva, Rita; Prosinecki, Vesna; Alexandre, Bruno M.; Carvalho, Ana S.; Matthiesen, Rune; Malhotra, Atul; Pinto, Paula; Bárbara, Cristina; Penque, DeborahWe have examined the effects of Obstructive Sleep Apnea (OSA) on red blood cell (RBC) proteome variation at evening/morning day time to uncover new insights into OSA-induced RBC dysfunction that may lead to OSA manifestations. Dysregulated proteins mainly fall in the group of catalytic enzymes, stress response and redox regulators such as peroxiredoxin 2 (PRDX2). Validation assays confirmed that at morning the monomeric/dimeric forms of PRDX2 were more overoxidized in OSA RBC compared to evening samples. Six month of positive airway pressure (PAP) treatment decreased this overoxidation and generated multimeric overoxidized forms associated with chaperone/transduction signaling activity of PRDX2. Morning levels of overoxidized PRDX2 correlated with polysomnographic (PSG)-arousal index and metabolic parameters whereas the evening level of disulfide-linked dimer (associated with peroxidase activity of PRDX2) correlated with PSG parameters. After treatment, morning overoxidized multimer of PRDX2 negatively correlated with fasting glucose and dopamine levels. Overall, these data point toward severe oxidative stress and altered antioxidant homeostasis in OSA RBC occurring mainly at morning time but with consequences till evening. The beneficial effect of PAP involves modulation of the redox/oligomeric state of PRDX2, whose mechanism and associated chaperone/transduction signaling functions deserves further investigation. RBC PRDX2 is a promising candidate biomarker for OSA severity and treatment monitoring, warranting further investigation and validation.
- Obstructive sleep apnea associated with Diabetes mellitus Type 2: a proteomic studyPublication . Vaz, Fátima; Valentim-Coelho, Cristina; Neves, Sofia; Feliciano, Amelia; Antunes, Marília; Pinto, Paula; Barbara, Cristina; Penque, DeborahBackground: We previously showed that Obstructive sleep apnea (OSA), a common public health concern causing deleterious cardiometabolic dysfunction, induced proteomic alterations in red blood cells (RBC) such as changes in the redox-oligomeric state of peroxiredoxin 2 (PRDX2)1-2. Herein, we aimed to investigate whether OSA patients with Type 2 Diabetes Mellitus before and after positive airway pressure (PAP) treatment present similar changes in the RBC antioxidant protein PRDX2 to better understand the molecular basic mechanisms associated with OSA and OSA outcomes. Methods: RBC samples from control snorers (n=22 being 3 diabetics) and OSA patients before and after six month of PAP-treatment (n=29 being 8 diabetics) were analysed by non-reducing western blot using antibody against PRDX2 or PRDXSO2/3 to measure the total and overoxidized levels of monomeric/dimeric/multimeric forms of PRDX2. Results: We confirmed previously data by showing that in OSA RBC the overoxidation on the monomeric forms of PRDX2 was higher compared to controls. After PAP treatment, this overoxidation decreased followed by an increase of multimeric-overoxidized forms of PRDX2 described to be associated with chaperone protective function. In contrast, the level of PRDX2 monomers in RBC diabetic OSA, although higher abundant its overoxidation level was much lower than those observed in OSA without comorbidity and did not significant change after treatment. Moreover, the level of PAP-induced PRDX2-overoxidized-multimers was also lower in these diabetic OSA patients. The level of overoxidized monomeric/dimeric forms of PRDX2 correlated negatively with levels of insulin / triglycerides and HbA1C, respectively. After PAP, the level of (overoxidized) PRDX2SO2/3 multimers correlated positively with adrenaline levels. Conclusions: The redox/oligomeric state of RBC PRDX2 that is regulated by overoxidation of the active cysteines was differentially modulated in diabetic OSA patients compared to OSA without this comorbidity. PAP-induced overoxidized oligo forms of PRDX2 that is associated with chaperone protective function showed decreased in OSA patients with diabetes. The clinical impact of these findings needs further investigation and validation.
- Obstructive sleep apnea syndrome: how are we in Portugal?Publication . Rodrigues, Ana Paula; Pinto, Paula; Nunes, Baltazar; Bárbara, CristinaIntroduction: Obstructive sleep apnea (OSA) is a breathing disorder with serious socio-economic consequences, being currently considered a public health problem, with patients at increased risk of cardiovascular diseases and traffic accidents. Despite the high prevalence of OSA reported in the literature is unknown the magnitude of OSA in Portugal, in particular, the number of cases currently diagnosed. Objectives: 1 To estimate the prevalence of OSA in the population of sentinel general practitioners (GP); 2 To identify factors potentially associated with severe OSA; 3. Characterize the diagnosis and treatment of OSA. Methods: Cross-sectional observational study in which sentinel physicians were invited to participate, by reporting all cases with a diagnosis of OSA (ICPC2 P16) registered on their lists of users. The scientific protocol and questionnaires were sent to physicians who agreed to participate. Results: A sample of 29 sentinel GP participated, with a population under observation of 46.685 users. 311 patients were identified with OSA (76.2% male) with a mean age of 62.8 years. No statistically significant differences between genders were observed. In the population under observation, the prevalence of OSA was 0.67% (CI 95%), being higher in males (1.07%). In the population aged above 25 years, there was a higher prevalence of OSA in both genders (0.89%), emphasizing the differences between genders (1.47% in males and 0.39 in female). The highest prevalence was observed in the age group 65 to 74 years (2.35%), being higher in males (4.02%). Underwent sleep study 97.7% of patients, which 56.2% performed polysomnography, the latter has been largely carried out in public institutions (89.1%). The average waiting time in public institutions was 6.8 months (0-36 months), compared to 1 month in private institutions (0-9 months). According to the severity of OSA, almost half of the patients (48.4%) with information on the apnea hypopnea index or respiratory disturbance index had severe OSA. Obesity (74.2%), hypertension (75.9%) and diabetes mellitus (34.1%) were the most frequent co-morbidities in these patients, verifying that being male (OR: 2.6) and having obesity (OR = 4.0) was associated with an increased risk of having severe OSA for all ages. 89.6% of patients were being treated with nasal CPAP, of which 96.1% had severe OSA and 85.2% had mild-moderate OSA, with a statistically significant difference. Among patients on CPAP, 62.8% were followed in specialized sleep consultation, and only 26.7% of patients who were not under CPAP were being followed in sleep consultation. Conclusion: In this population, the prevalence of OSA was similar to that reported in the literature in older age groups. Male gender and obesity were associated with an increased risk of severe OSA in all ages.
- Obstructive Sleep Apnea: a proteomics study of the effects of positive airway pressure therapyPublication . Valentim-Coelho, Cristina; Vaz, Fátima; Martins, Inês L.; Feliciano, Amélia; Pinto, Paula; Cristina, Bárbara; Penque, DeborahObstructive Sleep Apnea (OSA) syndrome is a common public health concern characterized by recurrent episodes of apneas and hypopneas during sleep. These obstructive events result in recurrent intermittent hypoxia and sleep fragmentation that can lead to metabolic and cardiovascular diseases. We recently demonstrated that OSA can cause alterations in the red blood cells (RBC) proteome that may be associated with OSA outcomes1,2. Here we intend to investigate whether the first-line therapy for OSA, the positive airway pressure (PAP) can revert or modulate these proteome alterations. RBCs from Snorers and patients with severe OSA before/after 6 months of PAP treatment (n=10/condition) were depleted of hemoglobin, analyzed by 2D-DIGE using Progenesis SameSpotsv4.5. The differentially abundant proteins were identified by MALDI-MS/MS and protein annotations acquired by DAVIDv6.8. Western blotting (WB) validation was performed for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and (overoxidized) GAPDHSO3 on a new Cohort (n=59). SPSS software was used to correlation studies with peroxiredoxin-2 (PRDX2) redox-oligomeric forms and several clinical parameters. Ten protein spots showed significant differences (Anova p<0.05) among groups and were associated with cell death, protein oligomerization and response to stress. Three proteoforms of GAPDH were identified decreased in OSA RBC (Anova p<0.05) and 6 months of PAP treatment increased these GAPDH proteoforms to the control levels. By WB, we confirmed these data by showing that the decreased GAPDH monomeric/tetrameric forms in OSA were increased by PAP treatment. PAP also increased GAPDHSO3 tetramers. In OSA, GAPDH monomers and GAPDHSO3 tetramers correlated positively with the respiratory disturbance index or triglycerides and adrenalin, respectively. After PAP, GAPDHSO3 tetramers correlated positively with PAP-induced PRDX2SO2/3 decameric forms, described having chaperone activity in cell protection. OSA induces alterations in the redox/oligomeric state of GAPDH and PRDX2 that can be reverted/modulated by PAP therapy. The clinical significant of these findings needs further validation and investigation.
- Obstructive Sleep Apnea: Epidemiology and Portuguese patients profilePublication . Rodrigues, Ana Paula; Pinto, Paula; Nunes, Baltazar; Bárbara, CristinaIntroduction: Obstructive Sleep Apnea (OSA) is characterized by recurrent episodes of apnea and hypopnea, secondary to collapse of the upper airways during sleep. OSA is frequently associated to cardiovascular complications. In Portugal, its magnitude is unknown. Methods: In 2014 a cross-sectional study was performed using the Portuguese General Practi- tioner (GP) Sentinel Network (Rede Médicos Sentinela). Participants GP reported all OSA cases diagnosed and registered in their lists of users on the 31 December 2013. Frequency of OSA has been estimated by sex and age. OSA patients were also characterized by method of diagnosis, treatment, and underlying conditions. Association between risk factors and severe OSA (odds ratio) was calculated using a logistic regression model adjusting confounding. Results: Prevalence of OSA on the population aged 25 years or more was 0.89% (95 CI: 0.80-1.00%); it was higher in males 1.47% (95 CI: 1.30-1.67%) and in those aged between 65 and 74 (2.35%). Most had severe OSA (48.4%). Hypertension (75.9%), obesity (74.2%) and diabetes mellitus (34.1%) were the most frequent comorbidities. Being a male (OR: 2.6; 95 CI: 1.2-5.8) and having obesity (OR: 4.0; 95 CI: 1.8-8.6) were associated with an increased risk of severe OSA. Conclusion: Found frequency of OSA was lower than other countries estimates, which may be explained by differences on case definition but can also suggest underdiagnosis of this condition as reported by other authors.
- Obstructive Sleep Apnea: New insights into antioxidant activity and cellular response to stressPublication . Vaz, Fátima; Feliciano, Amélia; Silva, Ana Rita; Coelho, Cristina; Torres, Vukosava Millic; Bozanic, Vesna; Malhotra, Atul; Pinto, Paula; Bárbara, Cristina; Penque, DeborahObstructive sleep apnea (OSA) is a sleep¬related breathing disorder characterized by recurrent episodes of apnea/and hypopnea during sleep with resultant intermittent hypoxia and sleep fragmentation, leading to cardiometabolic diseases. OSA affects 3.7% to 26% of adult population, but frequently is underdiagnosed. By 2DIGE-proteomics approach, we have investigated red blood cells (RBC) in OSA to uncover new insights into putative chronic stress-induced RBC dysfunction that lead to inflammation and metabolic syndrome associated with OSA. A number of proteins as potential candidate biomarkers for OSA, such as the cytosolic antioxidant regulators, catalase (CAT) and peroxiredoxin2 (PRX2) was identified, needing additional biochemical research validation.
- Overview of proteomics studies in obstructive sleep apneaPublication . Feliciano, Amélia; Torres, Vukosava M.; Vaz, Fatima; Carvalho, Ana Sofia; Matthiesen, Rune; Pinto, Paula; Malhotra, Atul; Bárbara, Cristina; Penque, DeborahObstructive sleep apnea (OSA) is an underdiagnosed common public health concern causing deleterious effects on metabolic and cardiovascular health. Although much has been learned regarding the pathophysiology and consequences of OSA in the past decades, the molecular mechanisms associated with such processes remain poorly defined. The advanced high-throughput proteomics-based technologies have become a fundamental approach for identifying novel disease mediators as potential diagnostic and therapeutic targets for many diseases, including OSA. Here, we briefly review OSA pathophysiology and the technological advances in proteomics and the first results of its application to address critical issues in the OSA field.
- Prevalência de síndrome de apneia obstrutiva do sono: um estudo da Rede Médicos-SentinelaPublication . Rodrigues, Ana Paula; Pinto, Paula; Nunes, Baltazar; Bárbara, CristinaEste estudo tem como objetivo estimar a prevalência de SAOS com diagnóstico conhecido na população sob observação da Rede Médicos-Sentinela (MS).
- Prevalência diagnosticada de Síndrome de Apneia Obstrutiva do Sono : dados da Rede Médicos-SentinelaPublication . Rodrigues, Ana Paula; Pinto, Paula; Nunes, Baltazar; Bárbara, CristinaIntrodução: A síndrome de apneia obstrutiva do sono (SAOS) caracteriza-se por episódios recorrentes de apneias e hipopneias, secundários ao colapso da via aérea superior no sono, encontrando-se associada a complicações cardiovasculares. Desconhece-se a sua magnitude em Portugal, nomeadamente, ao nível dos cuidados de saúde primários. Material e Métodos: Realizou-se um estudo transversal, no qual os Médicos-Sentinela participantes notificaram voluntariamente todos os casos com diagnóstico de SAOS das suas listas de utentes diagnosticados até 31 de Dezembro de 2013. Calculou-se a prevalência de SAOS desagregada por sexo e grupo etário, caracterizando-se os casos segundo sexo, idade, tipo de diagnóstico, tratamento e antecedentes pessoais. Para o estudo de associações entre fatores de risco de SAOS grave calcularam-se OR ajustados através um modelo de regressão logística. Resultados: A prevalência de SAOS na população com 25 ou mais anos de foi de 0,89 % (IC95% 0,80-1,00 %), sendo superior no sexo masculino 1,47 % (IC95% 1,30-1,67%) e no grupo etário entre os 65 e os 74 anos (2,35 %). A maioria tinha SAOS grave (48,5%). A obesidade (84,6%), hipertensão arterial (74,8%) e diabetes mellitus (38,7%) foram as co-morbilidades mais frequentes; ser do sexo masculino (OR: 2,6) e ter obesidade (OR: 4,0) associou-se a um maior risco de SAOS grave. Discussão: Observou-se uma prevalência menor do que a estimada noutros países o que pode estar relacionada com a definição de caso ou revelar um subdiagnóstico deste problema como é também referido por outros autores.