56 research outputs found

    New factors in heart failure pathophysiology : Immunity cells release of extracellular vesicles

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    Leukocyte-shed extracellular vesicles (EVs) can play effector roles in the pathophysiological mechanisms of different diseases. These EVs released by membrane budding of leukocytes have been found in high amounts locally in inflamed tissues and in the circulation, indicating immunity cell activation. These EVs secreted by immune cell subsets have been minimally explored and deserve further investigation in many areas of disease. In this study we have investigated whether in heart failure there is innate and adaptive immune cell release of EVs. Patients with chronic heart failure (cHF) (n = 119) and in sex- and age-matched controls without this chronic condition (n = 60). Specifically, EVs were quantified and phenotypically characterized by flow cytometry and cell-specific monoclonal antibodies. We observed that even in well medically controlled cHF patients (with guideline-directed medical therapy) there are higher number of blood annexin-V + (phosphatidylserine +)-EVs carrying activated immunity cell-epitopes in the circulation than in controls (p < 0.04 for all cell types). Particularly, EVs shed by monocytes and neutrophils (innate immunity) and by T-lymphocytes and natural-killer cells (adaptive immunity) are significantly higher in cHF patients. Additionally, EVs-shed by activated leukocytes/neutrophils (CD11b +, p = 0.006; CD29 + /CD15 +, p = 0.048), and T-lymphocytes (CD3 + /CD45 +, p < 0.02) were positively correlated with cHF disease severity (NYHA classification). Interestingly, cHF patients with ischemic etiology had the highest levels of EVs shed by lymphocytes and neutrophils (p < 0.045, all). In summary, in cHF patients there is a significant immune cell activation shown by high-release of EVs that is accentuated by clinical severity of cHF. These activated innate and adaptive immunity cell messengers may contribute by intercellular communication to the progression of the disease and to the common affectation of distant organs in heart failure (paracrine regulation) that contribute to the clinical deterioration of cHF patients

    Functional And Cognitive Decline Is Associated With Increased Endothelial Cell Inflammation And Platelet Activation. Liquid Biopsy Of Microvesicles In Community-Dwelling Octogenarians.

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    Increased life expectancy is usually associated with comorbidities, such as cardio andcerebrovascular disease causing impaired functionality. A common underlying cause ofthese comorbidities is vascular inflammation and injury. Elevated levels of circulatingmicrovesicles (cMV), as a product of a hemostatic and inflammatory cell activation,could be direct mapping of an imbalanced hemostasis. In this manuscript, we aimedto investigate by liquid biopsy whether successful aging can be discriminated bycMV levels and phenotype. To this purpose, we included 135 community-dwellingoctogenarians in a cross-sectional study. Successful aging was defined as goodfunctional (Barthel Index>90 points, and Lawton index score>7/4 points forwomen and men, respectively) and cognitive status (Spanish version of the Mini-Mental State Examination -MEC->24 points) and no need for institutionalization.Total, annexin V positive (AV+), and AV−cMV from different cell origins from thevascular compartment were phenotypically characterized and quantified from fastingplasma samples by flow cytometry. Successful aging was associated with lowerplasma concentrations of total and AV+CD141+/CD41+-CD61+, and PAC1+/AV+,CD141+/AV+, and CD36+/AV−cMV. From these phenotypes, ROC curve analysesrevealed that CD141+/AV+and CD141+/CD41+-CD61+/AV+endothelial- and platelet-derived cMV discriminate successful and non-successful aging with an AUC (95%CI) of0.655 (0.551, 0.758),P= 0.005, and 0.638 (0.535, 0.741),P= 0.013, respectively. In conclusion, successful aging is associated with low levels of cMV released by endothelialcells and platelets, indicating lower endothelial cell inflammation and platelet activation.Our results contribute to the understanding of the link between unsuccessful aging,cognitive decline and vascular cell inflammatory disturbances

    El lobo y su interacción con la ganadería

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    El lobo ibérico es una especie sujeta a diferentes consideraciones legales dentro de la Península Ibérica. Esta especie forma parte de la fauna típica de la península y es una figura importante en el ecosistema, así como también es un eslabón crucial en la cadena trófica. Sin embargo con frecuencia se considera incompatibe con la ganadería extensiva, ya que el lobo ha evolucionado para depredar a rumiantes vulnerables. El objetivo de este trabajo de fin de grado es en primer lugar aproximarnos al estudio del comportamiento de estos animales y analizar la situación del lobo y su interaccion con las actividades económicas en el medio rural, valorando las posibles medidas de mejora para su situación, protegiéndolo sin perjuicio de la ganadería

    A DIGE proteomic analysis of wheat flag leaf treated with TERRA-SORB® foliar, a free amino acid high content biostimulant

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    The flag leaf is the most important source of carbohydrate during wheat kernel filling. Around a 75% of all sugars stored in the kernel come from carbon fixed by this leaf. Terra-Sorb® foliar is an L-α-amino acid-based product from enzymatic hydrolysis for foliar application with a high ratio of free to total amino acids. Previous agronomical studies carried out on grassy, horticultural and tree crops have shown that the application of Terra-Sorb® increases photosynthetic plant activity and chlorophyll content, promotes rapid recovery from stress and improves fruit set. In this work, we have undertaken a proteomic approach to explore molecular mechanisms potentially involved in the stimulating effect of Terra-Sorb® Foliar on wheat yield when applied in commercial fields. Wheat plants at the flag leaf stage were treated, and a DIGE approach was used to compare the proteomes of treated vs. control plants in four biological replicates. Thirty-seven protein spots were found to change in abundance (ANOVA p<0.05) out of which 8 were down-regulated and 29 up-regulated in treated leaves. Twenty protein spots (1.2<fold change <1.9) encoded by 11 different genes were successfully identified by nLC-ESI-MS/MS and NCBInr database search. The deregulated proteins identified were mainly related to the life cycle of Rubisco. Importantly, two proteins involved in the positive regulation of Rubisco activity, namely Rubisco activase, and the large subunit of Rubisco binding protein, were found up-regulated in treated plants, suggesting a better performance of Rubisco. Down-regulated proteins were of metabolic and anti-stress enzymes, including Cu/Zn superoxide dismutase that protects photosystem 11 from photooxidation. In conclusion, significant changes were shown to occur in the wheat flag leaf proteome upon Terra-Sorb® Foliar application. The deregulated proteins identified are directly or indirectly involved in the C02 fixation which may correlate with the known stimulating effect of Terra-Sorb® Foliar of wheat yield, although further functional experiments are needed to validate the proposed hypothesis.This work was supported by Bioibérica, S.A. MJME acknowledged a grant contract from Fundación CajaMurcia-Universidad de Alicante

    Impacto de la edad del donante-receptor en la supervivencia al trasplante cardiaco. Subanálisis del Registro Español de Trasplante Cardiaco

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    [Abstract] Introduction and objectives. The age of heart transplant recipients and donors is progressively increasing. It is likely that not all donor-recipient age combinations have the same impact on mortality. The objective of this work was to compare survival in transplant recipients according to donor-recipient age combinations. Methods. We performed a retrospective analysis of transplants performed between 1 January 1993 and 31 December 2017 in the Spanish Heart Transplant Registry. Pediatric transplants, retransplants and combined transplants were excluded (6505 transplants included). Four groups were considered: a) donor < 50 years for recipient < 65 years; b) donor < 50 years for recipient ≥ 65 years; c) donor ≥ 50 years for recipient ≥ 65 years, and d) donor ≥ 50 years for recipient < 65 years. Results. The most frequent group was young donor for young recipient (73%). There were differences in the median survival between the groups (P < .001): a) younger-younger: 12.1 years, 95%CI, 11.5-12.6; b) younger-older: 9.1 years, 95%CI, 8.0-10.5; c) older-older: 7.5 years, 95%CI, 2.8-11.0; d) older-younger: 10.5 years, 95%CI, 9.6-12.1. On multivariate analysis, independent predictors of mortality were the age of the donor and the recipient (0.008 and 0.001, respectively). The worst combinations were older-older vs younger-younger (HR, 1.57; 95%CI, 1.22-2.01; P < .001) and younger-older vs younger-younger (HR, 1.33; 95%CI, 1.12-1.58; P = .001). Conclusions. Age (of the donor and recipient) is a relevant prognostic factor in heart transplant. The donor-recipient age combination has prognostic implications that should be identified when accepting an organ for transplant.[Resumen] Introducción y objetivos. La edad de receptores y donantes cardiacos se está incrementando progresivamente. Es probable que no todas las combinaciones tengan el mismo impacto en la mortalidad. El objetivo de este trabajo es comparar la supervivencia de los pacientes trasplantados según la combinación de edades de donante y receptor. Métodos. Análisis retrospectivo del Registro Español de Trasplante Cardiaco de los trasplantes realizados entre el 1 de enero de 1993 y el 31 de diciembre de 2017. Se excluyeron los pediátricos, los retrasplantes y los trasplantes combinados (se incluyeron 6.505 trasplantes). Se consideraron 4 grupos: a) donante menor de 50 años para receptor menor de 65 años; b) donante menor de 50 años para receptor de edad ≥ 65 años; c) donante de edad ≥ 50 años para receptor de 65 o más, y d) donante de edad ≥ 50 años para receptor menor de 65. Resultados. El grupo más frecuente fue el de donante joven para receptor joven (73%). Hubo diferencias en la mediana de supervivencia entre los grupos (p < 0,001): a) joven-joven: 12,1 años (IC95%, 11,5-12,6); b) joven-mayor: 9,1 años (IC95%, 8,0-10,5); c) mayor-mayor: 7,5 años (IC95%, 2,8-11,0), y d) mayor-joven: 10,5 años (IC95%, 9,6-12,1). En el análisis multivariante, las edades del donante y del receptor resultaron predictoras independientes de la mortalidad (0,008 y 0,001 respectivamente). Las peores combinaciones fueron mayor-mayor frente a joven-joven (HR = 1,57; IC95%, 1,22-2,01; p < 0,001) y joven-mayor frente a joven-joven (HR = 1,33; IC95%, 1,12-1,58; p = 0,001). Conclusiones. La edad (del donante y del receptor) es un factor pronóstico relevante en el trasplante cardiaco. La combinación de edades de donante y receptor posee implicaciones pronósticas que se debe conocer a la hora de aceptar un órgano para trasplante
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