Percorrer por autor "Pinho, Dora"
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- l-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in ratsPublication . Leal, Joana; Teixeira-Santos, Luísa; Pinho, Dora; Afonso, Joana; Carvalho, Jorge; de Lourdes Bastos, Maria; Albino-Teixeira, António; Fraga, Sónia; Sousa, TeresaWe evaluated whether l-proline (Pro) supplementation improves redox status and nitric oxide (NO) bioavailability and prevents or delays angiotensin II (AngII)-induced hypertension. Male Sprague-Dawley rats were distributed to four experimental groups: Pro + AngII (Pro-Ang), Pro + Saline (Pro-Sal), Vehicle + AngII (Veh-Ang) and Veh + Saline (Veh-Sal). Pro solution (2 g.kg-1·day-1) or water (vehicle) were orally administered, from day 0 to day 21. AngII (200 ng.kg-1.min-1) or saline were infused (s.c.) from day 7 to day 21. Systolic blood pressure (SBP) was measured by the tail-cuff method. From day 20-21, animals were kept on metabolic cages for 24h-urine collection. On day 21, urine and blood were collected for further quantification of redox status biomarkers, NO-related markers (urinary nitrates and nitrites, U-NOx; plasma asymmetric dimethylarginine, P-ADMA), metabolic and renal parameters. Pro prevented the AngII-induced SBP rise [mean (95% CI), Day 19: Pro-AngII, 137 (131; 143) vs. Veh-AngII, 157 (151; 163) mm Hg, P < 0.001]. Pro-AngII rats also had increased values of U-NOx, systemic and urinary total antioxidant status (TAS), urinary H2O2 and plasma urea, as well as reduced P-ADMA and unaltered urinary isoprostanes. Plasma Pro was inversely correlated with P-ADMA (r = -0.52, p = 0.0009) and positively correlated with urinary TAS (r = 0.55, p = 0.0005) which, in turn, was inversely correlated with P-ADMA (r = -0.56, p = 0.0004). Furthermore, urinary H2O2 values decreased across P-ADMA tertiles (p for linear trend = 0.023). These results suggest that Pro reduces P-ADMA levels and improves redox status, thereby increasing NO bioavailability and counteracting the AngII-induced SBP rise. H2O2 and TAS modulation by Pro may contribute to the reduced P-ADMA concentration.
- Resolvin E1-Chemerin receptor 1 axis is dysregulated in critical COVID-19 patientsPublication . Silva-Pereira, Carolina; Reina-Couto, Marta; Pereira-Terra, Patrícia; Teixeira-Santos, Luísa; Martins, Sandra; Pinho, Dora; Soares, Miguel Luz; Dias, Cláudia Camila; Sarmento, António; Tavares, Margarida; Guimarães, João Tiago; Paiva, José-Artur; Fraga, Sónia; Albino-Teixeira, António; Roncon-Albuquerque, Roberto; Sousa, TeresaResolvin E1 (RvE1) and Resolvin D1 (RvD1) are key resolvins implicated in inflammation resolution of respiratory and infectious diseases. In contrast to cytokines, they have been scarcely explored in COVID-19 and their ability for discriminating COVID-19 severity and patient outcomes has not been compared with that of cytokines. Therefore, among a panel comprising cytokines (interleukin (IL)-1beta, IL-6, IL-10, tumor necrosis factor alpha, interferon gamma and granulocyte-macrophage colony-stimulating factor), RvD1 and RvE1 and their respective receptors (FPR2, Chemerin1), we evaluated which mediators better distinguished COVID-19 severity, the need of mechanical ventilation and patient mortality. Blood was collected from 61 patients with “severe” (n = 27), “critical” (n = 17) and “critical on veno-venous extracorporeal membrane oxygenation (VV-ECMO)” (n = 17) COVID-19 at admission, days 3–4 and days 5–8, and from controls (n = 23) at a single time point. We measured cytokines by multiplex immunoassays, resolvins by enzyme-linked immunosorbent assays, and FPR2 and Chemerin1 mRNA by real-time quantitative polymerase chain reaction. We obtained principal component analysis (PCA)/partial least squares discriminant analysis (PLS-DA) models significantly differentiating (P < 0.001): controls from each patient group; “severe” from all critical patients; patients without or with mechanical ventilation, and survivors from non-survivors. RvE1 consistently showed a variable importance in projection (VIP) score > 2.5 and a p(corr) >0.8, being the most relevant discriminating variable. Univariate and repeated measures multivariate analyses showed higher RvE1 in “critical on VV-ECMO”, mechanically ventilated patients and non-survivors, while Chemerin1 exhibited an opposite profile. RvE1 positively correlated with inflammation and partial pressure of CO2, whereas Chemerin1 correlated with lower inflammation, better respiratory function and lower hospital length of stay. We conclude that RvE1 was the mediator best distinguishing COVID-19 severity and that RvE1-Chemerin1 axis is dysregulated in this disease.