Browsing by MeSH term "Heart Transplantation"
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Publication Critical warm ischemia time point for cardiac donation after circulatory death.(Munksgaard International Publishers, 2022-05) Sánchez-Cámara, Silvia; Asensio-López, Mari C; Royo-Villanova, Mario; Soler, Fernando; Jara-Rubio, Rubén; Garrido-Peñalver, Jose Francisco; Pinar, Eduardo; Hernández-Vicente, Álvaro; Hurtado, Jose Antonio; Lax, Antonio; Pascual-Figal, Domingo A; Fundación Mutua MadrileñaDonation after circulatory death (DCD) represents a promising opportunity to overcome the relative shortage of donors for heart transplantation. However, the necessary period of warm ischemia is a concern. This study aims to determine the critical warm ischemia time based on in vivo biochemical changes. Sixteen DCD non-cardiac donors, without cardiovascular disease, underwent serial endomyocardial biopsies immediately before withdrawal of life-sustaining therapy (WLST), at circulatory arrest (CA) and every 2 min thereafter. Samples were processed into representative pools to assess calcium homeostasis, mitochondrial function and cellular viability. Compared to baseline, no significant deterioration was observed in any studied parameter at the time of CA (median: 9 min; IQR: 7-13 min; range: 4-19 min). Ten min after CA, phosphorylation of cAMP-dependent protein kinase-A on Thr197 and SERCA2 decreased markedly; and parallelly, mitochondrial complex II and IV activities decreased, and caspase 3/7 activity raised significantly. These results did not differ when donors with higher WLST to CA times (≥9 min) were analyzed separately. In human cardiomyocytes, the period from WLST to CA and the first 10 min after CA were not associated with a significant compromise in cellular function or viability. These findings may help to incorporate DCD into heart transplant programs.Publication DC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance(Elsevier, 2015-06-16) Conde-San Román, Patricia; Rodriguez-Garcia, Mercedes; van der Touw, William; Jimenez, Ana; Burns, Matthew; Miller, Jennifer; Brahmachary, Manisha; Chen, Hui-ming; Boros, Peter; Rausell-Palamos, Francisco; Yun, Tae Jin; Riquelme, Paloma; Rastrojo, Alberto; Aguado, Begoña; Stein-Streilein, Joan; Tanaka, Masato; Zhou, Lan; Zhang, Junfeng; Lowary, Todd L; Ginhoux, Florent; Park, Chae Gyu; Cheong, Cheolho; Brody, Joshua; Turley, Shannon J; Lira, Sergio A; Bronte, Vincenzo; Gordon, Siamon; Heeger, Peter S; Merad, Miriam; Hutchinson, James; Chen, Shu-Hsia; Ochando, Jordi; Ministerio de Educación y Ciencia (España); Fundación Mutua MadrileñaTissue effector cells of the monocyte lineage can differentiate into different cell types with specific cell function depending on their environment. The phenotype, developmental requirements, and functional mechanisms of immune protective macrophages that mediate the induction of transplantation tolerance remain elusive. Here, we demonstrate that costimulatory blockade favored accumulation of DC-SIGN-expressing macrophages that inhibited CD8(+) T cell immunity and promoted CD4(+)Foxp3(+) Treg cell expansion in numbers. Mechanistically, that simultaneous DC-SIGN engagement by fucosylated ligands and TLR4 signaling was required for production of immunoregulatory IL-10 associated with prolonged allograft survival. Deletion of DC-SIGN-expressing macrophages in vivo, interfering with their CSF1-dependent development, or preventing the DC-SIGN signaling pathway abrogated tolerance. Together, the results provide new insights into the tolerogenic effects of costimulatory blockade and identify DC-SIGN(+) suppressive macrophages as crucial mediators of immunological tolerance with the concomitant therapeutic implications in the clinic.Publication Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance.(Elsevier, 2018) Braza, Mounia S; Garcia, Mercedes; Brahmachary, Manisha; Pothula, Venu; Fay, Francois; Boros, Peter; Werner, Sherry A; Ginhoux, Florent; Mulder, Willem J M; Ochando, Jordi; Conde-San Román, Patricia; Cortegano, Isabel; National Institutes of Health (Estados Unidos); Ministerio de Economía y Competitividad (España)The colony-stimulating factor 1 (CSF1) regulates the differentiation and function of tissue macrophages and determines the outcome of the immune response. The molecular mechanisms behind CSF1-mediated macrophage development remain to be elucidated. Here we demonstrate that neutrophil-derived CSF1 controls macrophage polarization and proliferation, which is necessary for the induction of tolerance. Inhibiting neutrophil production of CSF1 or preventing macrophage proliferation, using targeted nanoparticles loaded with the cell cycle inhibitor simvastatin, abrogates the induction of tolerance. These results provide new mechanistic insights into the developmental requirements of tolerogenic macrophages and identify CSF1 producing neutrophils as critical regulators of the immunological response.Publication Plasma-Derived Extracellular Vesicles as Potential Biomarkers in Heart Transplant Patient with Chronic Chagas Disease(Centers for Disease Control and Prevention (CDC), 2020-08) Cortes-Serra, Nuria; Mendes, Maria Tays; Mazagatos, Clara; Segui-Barber, Joan; Ellis, Cameron C; Ballart, Cristina; García-Álvarez, Ana; Gállego, Montserrat; Gascon, Joaquim; Almeida, Igor C; Pinazo, María Jesús; Fernandez-Becerra, Carmen; Ministerio de Ciencia, Innovación y Universidades (España); Fundación La Marató TV3; Fundación Mundo Sano; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); RETICS-Investigación colaborativa en Enfermedades Tropicales (RICET-ISCIII) (España); Red Iberoamericana Nuevas Herramientas para el Diagnóstico y la Evaluación del Paciente con Enfermedad de Chagas; NIH - National Institute on Minority Health and Health Disparities (NIMHD) (Estados Unidos); Government of Catalonia (España)Chagas disease is emerging in countries to which it is not endemic. Biomarkers for earlier therapeutic response assessment in patients with chronic Chagas disease are needed. We profiled plasma-derived extracellular vesicles from a heart transplant patient with chronic Chagas disease and showed the potential of this approach for discovering such biomarkers.