Beneficial effects of omega-3 fatty acids in the proteome of high-density lipoprotein proteome

BACKGROUND: Omega-3 poly-unsaturated fatty acids (ω-3 PUFAs) have demonstrated to be beneficial in the prevention of cardiovascular disease, however, the mechanisms by which they perform their cardiovascular protection have not been clarified. Intriguingly, some of these protective effects have also been linked to HDL. The hypothesis of this study was that ω-3 PUFAs could modify the protein cargo of HDL particle in a triglyceride non-dependent mode. The objective of the study was to compare the proteome of HDL before and after ω-3 PUFAs supplemented diet. METHODS: A comparative proteomic analysis in 6 smoker subjects HDL before and after a 5 weeks ω-3 PUFAs enriched diet has been performed. RESULTS: Among the altered proteins, clusterin, paraoxonase, and apoAI were found to increase, while fibronectin, α-1-antitrypsin, complement C1r subcomponent and complement factor H decreased after diet supplementation with ω-3 PUFAs. Immunodetection assays confirmed these results. The up-regulated proteins are related to anti-oxidant, anti-inflammatory and anti-atherosclerotic properties of HDL, while the down-regulated proteins are related to regulation of complement activation and acute phase response. CONCLUSIONS: Despite the low number of subjects included in the study, our findings demonstrate that ω-3 PUFAs supplementation modifies lipoprotein containing apoAI (LpAI) proteome and suggest that these protein changes improve the functionality of the particle

Coronary angioplasty produces alterations in the HDL proteome of patients with coronary disease

Comunicaciones a congreso

Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm

High-density lipoproteins (HDLs) are complex protein and lipid assemblies whose composition is known to change in diverse pathological situations. Analysis of the HDL proteome can thus provide insight into the main mechanisms underlying abdominal aortic aneurysm (AAA) and potentially detect novel systemic biomarkers. We performed a multiplexed quantitative proteomics analysis of HDLs isolated from plasma of AAA patients (N = 14) and control study participants (N = 7). Validation was performed by western-blot (HDL), immunohistochemistry (tissue), and ELISA (plasma). HDL from AAA patients showed elevated expression of peroxiredoxin-6 (PRDX6), HLA class I histocompatibility antigen (HLA-I), retinol-binding protein 4, and paraoxonase/arylesterase 1 (PON1), whereas alpha-2 macroglobulin and C4b-binding protein were decreased. The main pathways associated with HDL alterations in AAA were oxidative stress and immune-inflammatory responses. In AAA tissue, PRDX6 colocalized with neutrophils, vascular smooth muscle cells, and lipid oxidation. Moreover, plasma PRDX6 was higher in AAA (N = 47) than in controls (N = 27), reflecting increased systemic oxidative stress. Finally, a positive correlation was recorded between PRDX6 and AAA diameter. The analysis of the HDL proteome demonstrates that redox imbalance is a major mechanism in AAA, identifying the antioxidant PRDX6 as a novel systemic biomarker of AAA.We thank Simon Bartlett for language and scientific editing. This study was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) (SAF2016-80843-R, BIO2012-37926 and BIO2015-67580-P), Fondo de Investigaciones Sanitarias ISCiii-FEDER (PRB2) (IPT13/0001, ProteoRed, Redes RIC RD12/0042/00038 and RD12/0042/0056, Biobancos RD09/0076/00101 and CA12/00371), Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), and FRIAT. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505).S

Persistence of Anti-S1 IgG against SARS-CoV-2 eight months after the Booster dose of Vaccine in naive and previously infected healthcare workers

Our aim was to evaluate the immune response of healthcare workers included in the RIPOVAC study, after receiving a booster dose (third dose), in terms of intensity and persistence of induced antibodies. In the second phase of the RIPOVAC study, between December 2021 and January 2022, eight months after the second dose, 389 voluntary, immunocompetent, non-pregnant healthcare workers received a booster dose of SARS-CoV-2 vaccine, and a serum sample was obtained. Two groups of patients were established: with and without previous SARS-CoV-2 infection. In order to quantify anti-S1 IgG (AU/mL) we used CMIA (Abbott). All of the health workers were anti-S IgG positive 8 months after receiving the booster dose of the vaccine, with a mean of 17,040 AU/mL. In 53 patients without previous infection, antibody levels increased by a mean of 10,762 AU/mL. This figure is seven times higher than the one produced after the second dose (1506 AU/mL). The booster dose produces a robust elevation of the antibody level, which persists at 8 months, with levels significantly higher than those reached after the second dose, which allow one to predict a persistence of more than one year. The study demonstrates the efficacy of the booster dose of anti-SARS-CoV-2 vaccines

Older Adult Patients in the Emergency Department: Which Patients should be Selected for a Different Approach?

Background: While multidimensional and interdisciplinary assessment of older adult patients improves their short-term outcomes after evaluation in the emergency department (ED), this assessment is time-consuming and ill-suited for the busy environment. Thus, identifying patients who will benefit from this strategy is challenging. Therefore, this study aimed to identify older adult patients suitable for a different ED approach as well as independent variables associated with poor short-term clinical outcomes. Methods: We included all patients >= 65 years attending 52 EDs in Spain over 7 days. Sociodemographic, comorbidity, and baseline functional status data were collected. The outcomes were 30 -day mortality, re -presentation, hospital readmission, and the composite of all outcomes. Results: During the study among 96,014 patients evaluated in the ED, we included 23,338 patients >= 65 years-mean age, 78.4 +/- 8.1 years; 12,626 (54.1%) women. During follow-up, 5,776 patients (24.75%) had poor outcomes after evaluation in the ED: 1,140 (4.88%) died, 4,640 (20.51) returned to the ED, and 1,739 (7.69%) were readmitted 30 days after discharge following the index visit. A model including male sex, age >= 75 years, arrival by ambulance, Charlson Comorbidity Index >= 3, and functional impairment had a C -index of 0.81 (95% confidence interval, 0.80-0.82) for 30 -day mortality. Conclusion: Male sex, age >= 75 years, arrival by ambulance, functional impairment, or severe comorbidity are features of patients who could benefit from approaches in the ED different from the common triage to improve the poor short-term outcomes of this population

Safety and Revisit Related to Discharge the Sixty-one Spanish Emergency Department Medical Centers Without Hospitalization in Patients with COVID-19 Pneumonia. A Prospective Cohort Study UMC-Pneumonia COVID-19

Background: Information is needed on the safety and efficacy of direct discharge from the emergency department (ED) of patients with COVID-19 pneumonia. Objectives: The objectives of the study were to study the variables associated with discharge from the ED in patients presenting with COVID-19 pneumonia, and study ED revisits related to COVID-19 at 30 days (EDR30d). Methods: Multicenter study of the SIESTA cohort including 1198 randomly selected COVID patients in 61 EDs of Spanish medical centers from March 1, 2020, to April 30, 2020. We collected baseline and related characteristics of the acute episode and calculated the adjusted odds ratios (aOR) for ED discharge. In addition, we analyzed the variables related to EDR30d in discharged patients. Results: We analyzed 859 patients presenting with COVID-19 pneumonia, 84 (9.8%) of whom were discharged from the ED. The variables independently associated with discharge were being a woman (aOR 1.890; 95%CI 1.176-3.037), age 1200/mm(3) (aOR 4.667; 95%CI 1.045-20.839). The EDR30d of the ED discharged group was 40.0%, being lower in women (aOR 0.368; 95%CI 0.142-0.953). A total of 130 hospitalized patients died (16.8%) as did two in the group discharged from the ED (2.4%) (OR 0.121; 95%CI 0.029-0.498). Conclusion: Discharge from the ED in patients with COVID-19 pneumonia was infrequent and was associated with few variables of the episode. The EDR30d was high, albeit with a low mortality

Estudio del proteoma de la lipoporteína de alta densidad en diferentes situaciones clínicas

De los resultados obtenidos en el presente estudio se deducen las siguentes conclusiones principales: 1. El método de aislamiento de la HDL condiciona especialmente el tipo de partícula que se estudia. 2. El proteoma de la HDL en pacientes con CAD es muy variable y altamente dependiente del individuo. 3. La HDL, a través de las proteínas apoL1 y complemento C3, podría estar jugando un papel importante en la respuesta immune innata ante el daño tisular ocasionado por la angioplastia. La disminución de serotransferrina observada en la HDL tras la angioplastia podría proteger frente a las reacciones oxidativas catalizadas por el hierro liberado por la ruptura de la placa. 4. Los cambios funcionales globales observados en el proteoma de la HDL apoyan las funciones antitrombóticas y antiinflamatorias de la partícula. El aumento de proteínas de la coagulación en la HDL podría suponer la eliminación de las mismas del torrente y la contención de la coagulación y el desencadenamiento del fenómeno trombótico. La disminución de las proteínas de fase aguda conllevaría su distribución hacia el torrente donde podrían llevar a cabo la activación de la respuesta inflamatoria controlada necesaria para la protección del endotelio. Las proteínas de señalización podrían provenir directamente de la ruptura de las células presentes en la placa ateromatosa. 5. La partícula HDL podría ejercer de “almacén” de proteínas que serían rápidamente redistribuídas hacia el plasma ante una situación de inflamación y daño endotelial. La HDL podría estar ejerciendo de partícula recolectora de proteínas de desecho para su eliminación del torrente sanguíneo. 6. La partícula HDL en pacientes con HFC se encuentra enriquecida en proteínas de la coagulación y la respuesta de fase aguda. Además, presenta regulación anómala del sistema del complemento y un perfil de apolipoproteínas proaterosclerótico. 7. Los resultados sugieren que en HFC la partícula HDL podría ser disfuncional y proinflamatoria explicando el fenotipo y el riesgo cardiovascular de los pacientes. 8. Dosis bajas de ácidos grasos omega-3 no tienen efecto sobre la concentración lipídica pero son capaces de modificar el proteoma de la HDL, sugiriendo una mejora en la funcionalidad de la partícula en hombres fumadores. 9. Tras la suplementación dietética con ácidos grasos omega-3, se observó una disminución en la expresión de proteínas implicadas en la respuesta de fase aguda, la activación del sistema del complemento y la regulación de la activación plaquetaria. A su vez, se observó un aumento de expresión en proteínas asociadas con el metabolismo de lípidos, la coagulación, la señalización, la regulación de la proteólisis y la protección frente a la oxidación

Proyecto Segeda, de la investigación al desarrollo rural

Segeda Project (Zaragoza) has as an objective that the archaeological investigation is used for the rural development in which is incardinated. The historical relevance of Segeda has been the basis of celebrations of “the Idus” and “the Vulcanalia”, which were declared of Regional Tourist Interest. The archaeological discovery of a winery has resulted in the “Segeda Vitivinícola” (“Segeda Viticulture”) program with the construction in “Segeda Nova” of a winery and a wine cellar where wine “in a Celtiberian way” is being produced. The identification of a Celtiberian Sanctuary with clear astronomical orientations, together with the researches on Celtiberian cosmogony, is the basis of the “Cosmóbriga” program which has been started with a small planetarium where the visible cosmos from Segeda in 200 BC is observed.El Proyecto Segeda (Zaragoza) tiene como objetivo que la investigación arqueológica sirva para el desarrollo del ámbito rural en el que se desarrolla. La importancia histórica de Segeda ha sido la base de las celebraciones de “Los Idus” y “La Vulcanalia”, declaradas de Interés Turístico Regional. El descubrimiento arqueológico de un lagar ha dado lugar al programa “Segeda Vitivinícola”, con la construcción en el espacio de “Segeda Nova” de un lagar y una bodega donde se está elaborando vino “al modo celtibérico”. La identificación de un Santuario celtibérico con claras orientaciones astronómicas, unido a las investigaciones sobre la cosmogonía celtibérica, es la base del programa “Cosmóbriga”, iniciado con un pequeño planetario donde se observa el cosmos visible desde Segeda en el año 200 a. C

Beneficial effects of omega-3 fatty acids in the proteome of high-density lipoprotein proteome

Abstract Background Omega-3 poly-unsaturated fatty acids (ω-3 PUFAs) have demonstrated to be beneficial in the prevention of cardiovascular disease, however, the mechanisms by which they perform their cardiovascular protection have not been clarified. Intriguingly, some of these protective effects have also been linked to HDL. The hypothesis of this study was that ω-3 PUFAs could modify the protein cargo of HDL particle in a triglyceride non-dependent mode. The objective of the study was to compare the proteome of HDL before and after ω-3 PUFAs supplemented diet. Methods A comparative proteomic analysis in 6 smoker subjects HDL before and after a 5 weeks ω-3 PUFAs enriched diet has been performed. Results Among the altered proteins, clusterin, paraoxonase, and apoAI were found to increase, while fibronectin, α-1-antitrypsin, complement C1r subcomponent and complement factor H decreased after diet supplementation with ω-3 PUFAs. Immunodetection assays confirmed these results. The up-regulated proteins are related to anti-oxidant, anti-inflammatory and anti-atherosclerotic properties of HDL, while the down-regulated proteins are related to regulation of complement activation and acute phase response. Conclusions Despite the low number of subjects included in the study, our findings demonstrate that ω-3 PUFAs supplementation modifies lipoprotein containing apoAI (LpAI) proteome and suggest that these protein changes improve the functionality of the particle.</p