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Projeto de investigação
COVID-19 Vaccination - Emerging role of Red Blood Cells as immunomodulators
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Publicações
Second-hand smoke exposure modulates plasma proteins linked to detoxification, inflammation and atherothrombosis
Publication . Neves, Sofia; Pacheco, Solange A.; Vaz, Fátima; Valentim-Coelho, Cristina; Saraiva, Joana; James, Peter; Simões, Tânia; Penque, Deborah
Chronic exposure to second-hand smoke (SHS) contributes to the development of health issues, including cancer and cardiovascular diseases. Molecular mechanisms underlying SHS-related diseases remain poorly understood, highlighting the need for reliable risk assessment biomarkers. Herein, we demonstrate that the plasma proteome of individuals exposed to SHS undergoes significant modulation. Butyrylcholinesterase (BChE) and Vitamin D-binding protein (GC) that are involved in the physiological response to circulating toxic substances, as well as key mediators of systemic inflammation, including Complement C1r subcomponent (C1R), Complement C1q subcomponent subunit C (C1QC), Histidine-rich glycoprotein (HRG), and Vitamin K-dependent protein S (PROS1), were found to be significantly modulated in SHS-exposed individuals. Moreover, strong indicators of a pro-atherothrombotic response such Apolipoprotein A-IV (APOA4) and Alpha-2-antiplasmin (SERPINF2), were also differentially expressed. These findings provide novel insights into the biological pathways linking SHS-exposure to cardiovascular risks, and suggest a panel of candidate proteins with potential utility as SHS-risk assessment biomarkers.
Red blood cell proteomic profiling in mild and severe obstructive sleep apnea patients before and after positive airway pressure treatment
Publication . Valentim-Coelho, Cristina; Saraiva, Joana; Osório, Hugo; Antunes, Marília; Vaz, Fátima; Neves, Sofia; Pinto, Paula; Bárbara, Cristina; Penque, Deborah
Obstructive Sleep Apnea (OSA) is characterized by recurrent-episodes of apneas/hypopneas during sleep, leading to recurrent intermittent-hypoxia and sleep fragmentation. Non-treated OSA can result in cardiometabolic diseases. In this study, we applied a shotgun-proteomics strategy to deeper investigate the red blood cell-(RBC) homeostasis regulation in the context of OSA-severity and their response to six months of positive airway pressure (PAP)-treatment. RBC-samples from patients with Mild/Severe-OSA before/after-PAP treatment and patients as simple-snoring controls were selected. The mass-spectrometry raw-data was analysed by MaxQuant for protein identification/quantification followed by statistical Linear Models-(LM) and Linear Mixed Models-(LMM) to investigate OSA-severity effect and interaction with PAP, respectively. The functional/biological network analysis were performed by DAVID-platform. The results indicated that key-enzymes of the Embden-Meyerhof-Parnas (EMP)-glycolysis and pentose phosphate pathway-(PPP) were differentially changed in Severe-OSA, suggesting that the O2-dependent metabolic flux through EMP and PPP maybe compromised in these cells due to severe intermittent hypoxia/reoxygenation-induced oxidative-stress events in these patients. The Rapoport-Luebering-glycolytic shunt showed a significant downregulation across OSA-severity maybe to increase hemoglobin-O2 affinity to adapt to O2 low availability in the lung, although EMP-glycolysis showed decreased only in Severe-OSA. Proteins of the immunoproteasome were upregulated in Severe-OSA maybe to respond to severe oxidative-stress. In Mild-OSA, proteins related to the ubiquitination/neddylation-(Ub/Ned)-dependent proteasome system were upregulated. After PAP, proteins of Glycolysis and Ub/Ned-dependent proteasome system showed reactivated in Severe-OSA. In Mild-OSA, PAP induced upregulation of immunoproteasome proteins, suggesting that this treatment may increase oxidative-stress in these patients. Once validated these proteins maybe candidate biomarkers for OSA or OSA-therapy response.
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, Medical and health sciences ,Medical and health sciences/Health sciences
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Entidade financiadora
Fundação para a Ciência e a Tecnologia, I.P.
Programa de financiamento
Número da atribuição
2022.14435.BD