Barcelona Endothelium Team (BET)

  • Barcelona Endothelium Team
Campus Clinic-UB

Primary Hemostasis Laboratory
Hemotherapy-Hemostasis Department
3rd Floor, 3rd Staircase
Hospital Clinic de Barcelona
Villarroel, 170
08036 Barcelona

Phone (+34) 932 27 5400 Ext. 2034


The Barcelona Endothelium Team (BET) is a research group that has dedicated many years to the study of the endothelium and endothelial damage in various pathologies. One of our most productive lines is devoted to the characterization of endothelial damage in the context of both autologous and allogeneic hematopoietic stem cell transplantation (HSCT). In this framework, we are deepening our knowlege of the mechanisms involved in endothelial dysfunction, the role of the endothelium in the development of some complications observed after HSCT, and the search of pharmaceutical agents that could protect the endothelia and consequently prevent these complications.


The main objectives of BET group in the HSCT framework are:

  •  To characterize the endothelial damage produced because of the allo-reactivity phenomena occurring after allogeneic HSCT.
  • To elucidate which are the agents producing the endothelial damage observed during allogeneic HSCT.
  • To analyze the role of the endothelial damage in the development of some complications observed early after HSCT as veno-occlusive disease of the liver, capillary leak syndrome, thrombotic microangiopathy, engraftment syndrome, diffuse alveolar hemorrhage, and acute graft versus-host disease.
  • To investigate which agents can protect the endothelia during HSCT and consequently prevent these complications.


Dr. Ginés Escolar, Hospital Clínic de Barcelona, Universitat de Barcelona, Spain
Dra. Montserrat Rovira. SCT Unit. Hospital Clinic, Barcelona, Universitat de Barcelona, Spain
Prof. Dr. Ernst Holler, University Medical Centre, University of Regensburg, Germany
Prof. Dr. Günter Eissner, University College Dublin, Ireland
Jazz Pharmaceuticals Inc


Selected publications

Palomo M, Vera M, Martin S, Torramadé-Moix S, Martinez-Sanchez J, Belen Moreno A, Carreras E, Escolar G, Cases A, Díaz-Ricart M

Up-regulation of HDACs, a harbinger of uraemic endothelial dysfunction, is prevented by defibrotide.

J. Cell. Mol. Med. 28 Nov 2019, . Epub 28 Nov 2019
Endothelial dysfunction is an earlier contributor to the development of atherosclerosis in chronic kidney disease (CKD), in which the role of epigenetic triggers cannot be ruled out. Endothelial protective strategies, such as defibrotide (DF), may be useful in this scenario. We evaluated changes induced by CKD on endothelial cell proteome and explored the effect of DF and the mechanisms involved. Human umbilical cord vein endothelial cells were exposed to sera from healthy donors (n = 20) and patients with end-stage renal disease on haemodialysis (n = 20). Differential protein expression was investigated by using a proteomic approach, Western blot and immunofluorescence. HDAC1 and HDAC2 overexpression was detected. Increased HDAC1 expression occurred at both cytoplasm and nucleus. These effects were dose-dependently inhibited by DF. Both the HDACs inhibitor trichostatin A and DF prevented the up-regulation of the endothelial dysfunction markers induced by the uraemic milieu: intercellular adhesion molecule-1, surface Toll-like receptor-4, von Willebrand Factor and reactive oxygen species. Moreover, DF down-regulated HDACs expression through the PI3/AKT signalling pathway. HDACs appear as key modulators of the CKD-induced endothelial dysfunction as specific blockade by trichostatin A or by DF prevents endothelial dysfunction responses to the CKD insult. Moreover, DF exerts its endothelial protective effect by inhibiting HDAC up-regulation likely through PI3K/AKT.
More information
Martinez-Sanchez J, Hamelmann H, Palomo M, Mir E, Moreno-Castaño AB, Torramade S, Rovira M, Escolar G, Cordes S, Kalupa M, Mertlitz S, Riesner K, Carreras E, Penack O, Diaz-Ricart M

Acute Graft-vs.-Host Disease-Associated Endothelial Activation

Front Immunol 2019, 10 2339. Epub 9 Oct 2019
Angiogenesis and endothelial activation and dysfunction have been associated with acute graft-vs.-host disease (aGVHD), pointing to the endothelium as a potential target for pharmacological intervention. Defibrotide (DF) is a drug with an endothelium-protective effect that has been approved for the treatment of veno-occlusive disease/sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation. Clinical data suggest that DF also reduces the incidence of aGVHD; however, the mechanisms of DF-mediated aGVHD regulation have not been examined. To investigate possible DF-mediated prophylactic and therapeutic mechanisms in aGVHD, we performed
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Mir E, Palomo M, Rovira M, Pereira A, Escolar G, Penack O, Holler E, Carreras E, Diaz-Ricart M

Endothelial damage is aggravated in acute GvHD and could predict its development.

Bone Marrow Transplant. Sep 2017, 52 (9) 1317-1325. Epub 26 Jun 2017
The aim of the present study was to explore whether there is enhanced endothelial dysfunction in patients developing acute GvHD (aGvHD) after allogeneic hematopoietic cell transplantation (allo-HCT) and to identify biomarkers with predictive and/or diagnostic value. In in vitro experiments, endothelial cells (ECs) were exposed to serum from patients with (aGvHD, n=31) and without (NoGvHD, n=13) aGvHD, to evaluate changes in surface adhesion receptors, the reactivity of the extracellular matrix by measuring the presence of Von Willebrand factor (VWF) and platelet adhesion, and the activation of intracellular signaling proteins. Plasma levels of VWF, ADAMTS-13, TNF receptor 1 (TNFR1), soluble vascular cell adhesion molecule 1 and soluble intercellular adhesion molecule 1 were also measured. In vitro results showed a more marked proinflammatory and prothrombotic phenotype in ECs in association with aGvHD. Regarding circulating biomarkers, levels of VWF and TNFR1 above an optimal cutoff score, taken independently or combined, at day 7 after allo-HCT, would be able to positively predict that around 90% of patients will develop aGvHD. Our results demonstrate that endothelial damage is aggravated in those allo-HCT recipients developing aGvHD, and that VWF and TNFR1 are promising predictive aGvHD biomarkers. These findings could contribute to improve the understanding of the pathophysiology of aGvHD.
More information
Palomo M, Blasco M, Molina P, Lozano M, Praga M, Torramade-Moix S, Martinez-Sanchez J, Cid J, Escolar G, Carreras E, Paules C, Crispi F, Quintana LF, Poch E, Rodas L, Goma E, Morelle J, Espinosa M, Morales E, Avila A, Cabello V, Ariceta G, Chocron S, Manrique J, Barros X, Martin N, Huerta A, Fraga-Rodriguez GM, Cao M, Martin M, Romera AM, Moreso F, Manonelles A, Gratacos E, Pereira A, Campistol JM, Diaz-Ricart M

Complement Activation and Thrombotic Microangiopathies.

Clin J Am Soc Nephrol 6 Nov 2019, . Epub 6 Nov 2019
Atypical hemolytic uremic syndrome is a form of thrombotic microangiopathy caused by dysregulation of the alternative complement pathway. There is evidence showing complement activation in other thrombotic microangiopathies. The aim of this study was to evaluate complement activation in different thrombotic microangiopathies and to monitor treatment response.
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Palomo M, Mir E, Rovira M, Escolar G, Carreras E, Diaz-Ricart M

What is going on between defibrotide and endothelial cells? Snapshots reveal the hot spots of their romance.

Blood 11 Jan 2016, . Epub 11 Jan 2016
Defibrotide (DF) has received EMA authorization to treat sinusoidal obstruction syndrome, an early complication after hematopoietic cell transplantation. DF has a recognized role as an endothelial protective agent, although its precise mechanism of action remains to be elucidated. The aim of the present study was to investigate the interaction of DF with endothelial cells (ECs). A human hepatic endothelial cell line was exposed to different DF concentrations, previously labelled. Using inhibitory assays and flow cytometry techniques along with confocal microscopy, we explored: DF-EC interaction, endocytic pathways, and internalization kinetics. Moreover, we evaluated the potential role of adenosine receptors in DF-EC interaction and if DF effects on endothelium were dependent of its internalization. Confocal microscopy showed interaction of DF with EC membranes followed by internalization, though DF did not reach cell nucleus even after 24h. Flow cytometry revealed concentration, temperature and time dependent up-take of DF in two EC models but not in other cell types. Moreover, inhibitory assays indicated that entrance of DF into ECs occurs primarily through macropinocytosis. Our experimental approach did not show any evidence of the involvement of adenosine receptors in DF-EC interaction. The anti-inflammatory and antioxidant properties of DF seem to be due to the interaction of the drug with the cell membrane. Our findings contribute to a better understanding of the precise mechanisms of action of DF as a therapeutic and potential preventive agent on the endothelial damage underlying different pathological situations.
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Current projects

Deepening the knowledge of Defibrotide.

Project leader:Enric Carreras
Start date:01/10/2010
End date:31/12/2016

Previous projects

Disfunción endotelial en el trasplante de progenitores hematopoyéticos: caracterización biológica y papel en las principales complicaciones precoces pos-trasplante

Project leader:Enric Carreras
Code:FIS PI050153
Start date:23/07/2005
End date:31/12/2008

Disfunción endotelial post-trasplante hematopoyético. Impacto de los agentes empleados en el régimen de acondicionamiento y análisis de posibles agentes protectores.

Project leader:Enric Carreras
Code:FIS PI000156
Start date:01/01/2008
End date:31/12/2011

Characterization of endothelial dysfunction that develops in haematopoietic stem cell transplantation: role in the main complications appearing early after transplantation

Project leader:Enric Carreras
Start date:31/01/2008
End date:31/03/2011