91 research outputs found
Notch-mediated cellular interactions between vascular cells
No full textVessel formation and differentiation to a proper hierarchical vasculature requires a coordinated effort from endothelial and mural cells. Over the last decade Notch was identified as a key player in this process by promoting vascular arterialization and modulating endothelial tip-stalk phenotypes. Recent work has identified that Notch fine-tunes the diverse endothelial phenotypes through regulation of canonical cell-cycle and metabolism regulators, such as ERK and Myc. During arterialization, Notch signaling inhibits the cell-cycle and metabolism of endothelial cells which coincides with the acquisition of arterial identity. During angiogenesis, the same molecular machinery prevents the hypermitogenic arrest and excessive sprouting of vessels. Notch also signals in pericytes and smooth muscle cells promoting vascular coverage and maturation. Here, we will review the latest findings on how Notch signals regulate the differentiation and interactions among vascular cells during organ development and homeostasis.Rui Benedito’s laboratory was supported by the European Research
Council (ERC) Consolidator Grant AngioUnrestUHD (101001814), the
Ministerio de Ciencia e Innovacio´n (PID2020-120252RB-I00) and “la
Caixa” Banking Foundation (HR22-00316). Henar Cuervo’s research was
supported by the Atraccio´n de Talento funding from the Comunidad
Auto´noma de Madrid (2020-T1/BMD-19985).S
Macrophages
No full textIn Chagas disease, which is caused by Trypanosoma cruzi, macrophages and cardiomyocytes are the main targets of infection. Classical activation of macrophages during infection is protective, whereas alternative activation of macrophages is involved in the survival of host cells and parasites. We studied the expression of inducible nitric oxide synthase (iNOS) and arginase as markers of classical and alternative activation, respectively, in heart tissue during in vivo infection of BALB/c and C57BL/6 mice. We found that expression of arginase I and II, as well as that of ornithine decarboxylase, was much higher in BALB/c mice than in C57BL/6 mice and that it was associated with the parasite burden in heart tissue. iNOS and arginase II were expressed by cardiomyocytes. Interestingly, heart-infiltrated CD68+ macrophages were the major cell type expressing arginase I. T helper (Th) 1 and Th2 cytokines were expressed in heart tissue in both infected mouse strains; however, at the peak of parasite infection, the balance between Th1 and Th2 predominantly favored Th1 in C57BL/6 mice and Th2 in BALB/c mice. The results of the present study suggest that Th2 cytokines induce arginase expression, which may influence host and parasite cell survival but which might also down-regulate the counterproductive effects triggered by iNOS in the heart during infection.Fil: Cuervo, Henar. Universidad Autónoma de Madrid; EspañaFil: Pineda, Miguel A.. Universidad Autónoma de Madrid; EspañaFil: Aoki, Maria del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Gea, Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Fresno, Manuel. Universidad Autónoma de Madrid; EspañaFil: Gironès, Núria. Universidad Autónoma de Madrid; Españ
Vascular biology 2014 in Monterey, California: celebrating 20 years of NAVBO
No full textA meeting report for Vascular Biology 2014, held in Monterey, California and organized by the North American Vascular Biology Organization (NAVBO)
Trypanosoma cruzi infection and endothelin-1 cooperatively activate pathogenic inflammatory pathways in cardiomyocytes
No full textTrypanosoma cruzi, the causative agent of Chagas disease, induces multiple responses in the heart, a critical organ of infection and pathology in the host. Among diverse factors, eicosanoids and the vasoactive peptide endothelin-1 (ET-1) have been implicated in the pathogenesis of chronic chagasic cardiomyopathy. In the present study, we found that T. cruzi infection in mice induces myocardial gene expression of cyclooxygenase-2 (Cox2) and thromboxane synthase (Tbxas1) as well as endothelin-1 (Edn1) and atrial natriuretic peptide (Nppa). T. cruzi infection and ET-1 cooperatively activated the calcium/calcineurin (Cn)/nuclear factor of activated T cells (NFAT) signaling pathway in atrial myocytes, leading to COX-2 protein expression and increased eicosanoid (prostaglandins E2 and F2 alpha, thromboxane A2) release. Moreover, T. cruzi infection of ET-1-stimulated cardiomyocytes resulted in significantly enhanced production of atrial natriuretic peptide (ANP), a prognostic marker for impairment in cardiac function of chagasic patients. Our findings support an important role for the calcium/Cn/NFAT cascade in T. cruzi-mediated myocardial production of inflammatory mediators and may help define novel therapeutic targets.Fil: Corral, Ricardo Santiago. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutierrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guerrero, Néstor A.. Consejo Superior de Investigaciones Cientificas; España. Universidad Autonoma de Madrid. Hospital Universitario de la Princesa; EspañaFil: Cuervo, Henar. Consejo Superior de Investigaciones Cientificas; EspañaFil: Gironès, Núria. Consejo Superior de Investigaciones Cientificas; España. Universidad Autonoma de Madrid. Hospital Universitario de la Princesa; EspañaFil: Fresno, Manuel. Consejo Superior de Investigaciones Cientificas; España. Universidad Autonoma de Madrid. Hospital Universitario de la Princesa; Españ
L-arginine metabolism in experimental Chagas disease: role of arginase I and iNOS in heart tissue=Metabolismo de la L-arginina en la enfermedad de Chagas experimental: papel de la arginasa I y la iNOS en tejido cardiaco
No full textTesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular . Fecha de lectura: 25-04-200
Percepción de la violencia en los adolescentes en el último curso de Secundaria. Intervención a través de la educación artística para una educación equitativa
No full textTesis realizada en la Universidad de OviedoLa visita a la exposición “A pesar de todo dibujan…” motivó el desarrollo de esta tesis que explora la percepción que el estudiantado adolescente tiene de las conductas violentas y sus manifestaciones para plantear una intervención que genere una conciencia crítica y potencie unas habilidades que permitan al alumnado enfrentarse a la violencia del entorno.MINISTERIO DE CIENCIA, INNOVACIÓN Y UNIVERSIDADES * FECYT * UCC+
Percepción de la violencia en los adolescentes en el último curso de secundaria. Intervención a través de la educación artística para una educación equitativa
No full textCon esta investigación se pretende realizar un acercamiento al conocimiento de la percepción de violencia que tiene el adolescente en su entorno más próximo. Este conocimiento será clave en la elaboración de una intervención a través de la educación artística que pretende dotar al adolescente de capacidad crítica ante la “cultura de violencia”. Los problemas de autoestima pueden ser un factor de riesgo frente a la violencia (Palomero y Fernández, 2001), por lo tanto, es importante, fortalecer la autoestima del adolescente, siendo nuestra propuesta, llevarlo a cabo a través de la creación artística con constantes referencias a la producción artística del siglo XX y XXI
Deficiency of Notch signaling in pericytes results in arteriovenous malformations
No full textArteriovenous malformations (AVMs) are high-flow lesions directly connecting arteries and veins. In the brain, AVM rupture can cause seizures, stroke, and death. Patients with AVMs exhibit reduced coverage of the vessels by pericytes, the mural cells of microvascular capillaries; however, the mechanism underlying this pericyte reduction and its association with AVM pathogenesis remains unknown. Notch signaling has been proposed to regulate critical pericyte functions. We hypothesized that Notch signaling in pericytes is crucial to maintain pericyte homeostasis and prevent AVM formation. We inhibited Notch signaling specifically in perivascular cells and analyzed the vasculature of these mice. The retinal vessels of mice with deficient perivascular Notch signaling developed severe AVMs, together with a significant reduction in pericytes and vascular smooth muscle cells (vSMC) in the arteries, while vSMCs were increased in the veins. Vascular malformations and pericyte loss were also observed in the forebrain of embryonic mice deficient for perivascular Notch signaling. Moreover, the loss of Notch signaling in pericytes downregulated Pdgfrb levels and increased pericyte apoptosis, pointing to a critical role for Notch in pericyte survival. Overall, our findings reveal a mechanism of AVM formation and highlight the Notch signaling pathway as an essential mediator in this process
Passive Beam Field Characterization for Application in Radiobiology
No full textThe main challenge of radiotherapy, used for treating cancer, is to deposit the prescribed dose in the tumor volume while sparing the surrounding tissue.The depth-dose distribution of protons makes proton therapy an alternative to conventional radiotherapy for some tumor sites. A better knowledge of the proton radiobiological mechanisms can improve the effectiveness of radiotherapy treatments.Holland Proton Therapy Center (HPTC) is one of the Dutch proton therapy centers. One of the purposes of its experimental beamline is to perform radiobiological experiments. To conduct different types of pre-clinical experiments, the beamline must be equipped to provide large field irradiation with precise dose characterization. Moreover, having a reliable Monte Carlo(MC) model of the system allows to perform in silico verification of the beamline design and contribute to its optimization. In this context, the goals of this project were: implementing a dual-ring scattering system in the experimental room of HPTC to produce homogeneous fields of different sizes; creating a MC model of the HPTC passive beamline able to reproduce the experimental setup.A dual-ring double scattering system was implemented in the HPTC horizontal beamline, starting from a single 150MeV pencil beam. The resulting passive irradiation fields were characterized by measuring and analyzing the lateral beam profiles, the depth-dose distributions and the relative dose at target position. Moreover, the beam characteristics and setup were implemented in theTOPAS MC code. The beam source parameters, input of the MC model, were found by comparing the experimental and simulated beam envelope and depth-dose distributions of the pencil beam. Then, the passive system model was benchmarked with experimental data by evaluating the lateral profiles, Braggcurves and dose distributions.The results show that the implemented passive system can achieve dose uniformity between 96% and 99% for field sizes between 4x4cm2 and 20x20cm2for a 150 MeV proton beam. Moreover, using a collimator with a 5x5cm2aperture, uniformity of at least 97% in the different Bragg peak regions is achieved. Good uniformity is also obtained for beam energies in the range 115MeV-150 MeV, showing robustness of the setup. Furthermore, the range of the proton beams traversing the beam-shaping elements, as well as the energy arriving to target, were studied. Moreover, with a ridge modulator, Spread-OutBragg peaks were obtained with a width up to 3,4cm and of uniformity 98,5%.The MC model produced in TOPAS was first benchmarked against a 150MeVproton beam in air. Secondly, the experimental data of the large fields were compared with the simulated ones. The simulation of depth-dose distributions and lateral beam profiles agreed with the experimental data. Furthermore, the model was used to estimate the number of initial protons required to achieve an experimental dose and to estimate the location of the Bragg peaks.All in all, the dual-ring passive scattering setup has been successfully implemented and is ready to be used to perform radiobiological experiments. Also, the TOPAS MC model can be used to assist in the preparation of these experiments and to further optimize the beamline design.Biomedical Engineerin
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