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Evening and morning peroxiredoxin-2 redox/oligomeric state changes in obstructive sleep apnea red blood cells : correlation with polysomnographic and metabolic parameters
Publication . Feliciano, Amélia; Vaz, Fátima; Torres, Vukosava M.; Coelho, Cristina Valentim; Silva, Rita; Prosinecki, Vesna; Alexandre, Bruno M.; Carvalho, Ana S.; Matthiesen, Rune; Malhotra, Atul; Pinto, Paula; Bárbara, Cristina; Penque, Deborah
We 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.
Hematological evaluation in males with obstructive sleep apnea before and after positive airway pressure
Publication . Feliciano, A.; Linhas, R.; Marçôa, R.; Cysneiros, A.; Martinho, C.; Reis, R. P.; Penque, D.; Pinto, P.; Bárbara, C.
Obstructive sleep apnea syndrome (OSAS) is a systemic inflammatory disease associated with cardiovascular consequences. Red blood cell distribution width (RDW), mean platelet volume (MPV), and platelet distribution width (PDW) are recognized biomarkers of cardiovascular morbidity/mortality. Limited data is available on the association between these parameters and OSAS severity and the relationship with positive airway pressure therapy (PAP). In this prospective study of male OSAS patients we analyzed hematological data in order to evaluate their value in predicting OSAS severity, the relationship with sleep parameters, and their behavior under PAP. Seventy-three patients were included (mean age 46.5 years), of which 36 were mild (49.3%), 10 moderate (13.7%), and 27 severe (37%). The mean RDW increased significantly with OSAS severity and showed a positive correlation with respiratory disturbance index and hypoxemic burdens. Additionally, a group of 48 patients (mean age 47.2 years) were submitted to PAP. After six months, red blood cell count, hemoglobin, hematocrit, and platelet count showed a significant decrease (p<0.0001; p<0.0001; p=0.001; p<0.0001; respectively). Concerning OSAS severity, these parameters also significantly decreased in mild patients (p=0.003; p=0.043; p=0.020; p=0.014; respectively) but only hemoglobin, hematocrit, and platelet count decreased in severe cases (p<0.0001; p=0.008; p=0.018; respectively). This study demonstrated an association between RDW values and OSAS severity. Moreover, red cell and platelet parameters changed significantly after PAP, supporting its cardiovascular protective effect. RDW may become a simple/inexpensive blood biomarker, making it useful in prioritizing OSAS patients waiting for polysomnography, and red cell and platelet parameters could be useful in PAP follow up.
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Fundação para a Ciência e a Tecnologia
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3599-PPCDT
Número da atribuição
HMSP-ICJ/0022/2011