Protective Effect of Defibrotide on Perfusion Induced Endothelial Damage

2000 ◽  
Vol 99 (4) ◽  
pp. 335-341 ◽  
Author(s):  
Tangül Şan ◽  
Hadi Moini ◽  
Kaya Emerk ◽  
Serpil Bilsel
Keyword(s):  
Protective Effect ◽  
Endothelial Damage

Protective Effect of Vitamin E on Immune Triggered, Granulocyte Mediated Endothelial Injury

1984 ◽  
Vol 51 (01) ◽  
pp. 089-092 ◽  
Author(s):  
M A Boogaerts ◽  
J Van de Broeck ◽  
H Deckmyn ◽  
C Roelant ◽  
J Vermylen ◽  
...  
Keyword(s):  
Vitamin E ◽  
Protective Effect ◽  
Umbilical Vein ◽  
Endothelial Damage ◽  
Endothelial Injury ◽  
Mediated Effects ◽  
Anti Oxidant ◽  
Endothelial Cell Cultures ◽  
Vitro Model

SummaryThe effect of alfa-tocopherol on the cell-cell interactions at the vessel wall were studied, using an in vitro model of human umbilical vein endothelial cell cultures (HUEC). Immune triggered granulocytes (PMN) will adhere to and damage HUEC and platelets enhance this PMN mediated endothelial injury. When HUEC are cultured in the presence of vitamin E, 51Cr-leakage induced by complement stimulated PMN is significantly decreased and the enhanced cytotoxicity by platelets is completely abolished (p <0.001).The inhibition of PMN induced endothelial injury is directly correlated to a diminished adherence of PMN to vitamin E- cultured HUEC (p <0.001), which may be mediated by an increase of both basal and stimulated endogenous prostacyclin (PGI2) from alfa-tocopherol-treated HUEC (p <0.025). The vitamin E-effect is abolished by incubation of HUEC with the irreversible cyclo-oxygenase inhibitor, acetylsalicylic acid, but the addition of exogenous PGI2 could not reproduce the vitamin E-mediated effects.We conclude that vitamin E exerts a protective effect on immune triggered endothelial damage, partly by increasing the endogenous anti-oxidant potential, partly by modulating intrinsic endothelial prostaglandin production. The failure to reproduce vitamin E-protection by exogenously added PGI2 may suggest additional, not yet elucidated vitamin E-effects on endothelial metabolism.

Abstract 135: Endothelial Dysfunction in Acute Graft-versus-host Disease After Allogeneic Hematopoietic Cell Transplantation. In vitro Evidence of the Protective Effect of Defibrotide

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Enrique Mir ◽  
Marta Palomo ◽  
Enric Carreras ◽  
Maribel Diaz-Ricart ◽  
Montse Rovira ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Protective Effect ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Endothelial Damage ◽  
Hematopoietic Cell ◽  
Graft Versus Host ◽  
Acute Graft

Acute Graft-Versus-Host Disease (aGVHD) is the most common early complication after allogeneic Hematopoietic Cell Transplantation (allo-HCT). We demonstrated endothelial dysfunction (ED) in association with allo-HCT. According to this data, aGVHD has been linked to an inflammatory process that may affect the endothelium. To investigate the differential degree of endothelial damage in patients developing or not aGVHD, to identify potential biomarkers, and to explore the protective effect of defibrotide (DF) in this scenario. DF has orphan designation for GVHD prevention. Patients blood samples were collected before allo-HCT, at day 0, and every week till day 28 after HCT. Plasma proteins (sTNFR1, sVCAM-1, VWF and ADAMTS-13) were measured as biomarkers of ED in individual samples from patients developing (GVHD, n=24), or not (NoGVHD, n=13), aGVHD. In in vitro assays, endothelial cells (EC) in culture were exposed to media containing pooled sera from patients to evaluate changes in the: a) expression of VCAM-1 and ICAM-1 on cell surfaces; b) presence of VWF on the extracellular matrix (ECM) and c) reactivity of the ECM towards platelets, under flow. The effect of DF was explored in the in vitro experiments by previous exposure of the EC (for 24h) followed by continuous incubation (100 μg/ml, added every 24h). Levels of sTNFRI, sVCAM-1 and VWF in samples from group GVHD were significantly higher than in NoGVHD (increases of 100, 37 and 150% respectively, at diagnose, p<0.01). ADAMTS-13 activity and VWF levels were inversely related. In in vitro studies, cell surface expression of VCAM-1 and ICAM-1, presence of VWF and platelet adhesion on the ECM in response to GVHD samples were always superior (increases vs NoGVHD of 80, 40, 100 and 21%, respectively, at diagnose). In vitro exposure of EC to DF attenuated signs of endothelial injury reducing significantly (p<0.05) the expression of VCAM-1, ICAM-1 and VWF (reductions of 22, 30 and 30%, respectively) in the GVHD condition. Our results demonstrate endothelial damage in association with aGVHD, as evidenced by elevated plasma levels of several biomarkers. The in vitro approach showed a marked proinflammatory and prothrombotic phenotype in association with aGVHD, which could be significantly prevented by defibrotide.

Protective effect of a newly developed fucose-deficient recombinant antithrombin against histone-induced endothelial damage

2018 ◽  
Vol 107 (5) ◽  
pp. 528-534 ◽  
Author(s):  
Toshiaki Iba ◽  
Tatsuhiko Hirota ◽  
Koichi Sato ◽  
Isao Nagaoka
Keyword(s):  
Protective Effect ◽  
Endothelial Damage

Protective effect of free-radical scavengers on corneal endothelial damage in phacoemulsification

2007 ◽  
Vol 33 (2) ◽  
pp. 310-315 ◽  
Author(s):  
Arie Y. Nemet ◽  
Ehud I. Assia ◽  
Dan Meyerstein ◽  
Naomi Meyerstein ◽  
Aharon Gedanken ◽  
...  
Keyword(s):  
Free Radical ◽  
Protective Effect ◽  
Endothelial Damage ◽  
Free Radical Scavengers ◽  
Radical Scavengers

Evidence of Defibrotide Internalization and Its Protective Effect in a Hepatic Endothelial in Vitro model

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5960-5960
Author(s):  
Maribel Diaz-Ricart ◽  
Marta Palomo ◽  
Enric Mir ◽  
Montserrat Rovira ◽  
Gines Escolar ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Protective Effect ◽  
Mtt Assay ◽  
Research Funding ◽  
Cell Membranes ◽  
Hematopoietic Cell Transplantation ◽  
Mechanisms Of Action ◽  
Endothelial Damage

Abstract INTRODUCTION: Defibrotide (DF) interferes with several steps of the coagulation-inflammation cycle. Last October (2013), DF received EMA authorization for its use in the treatment of severe hepatic veno-occlusive disease (VOD) after hematopoietic cell transplantation (HCT). Since endothelial dysfunction has been associated with the development of VOD, among other HCT complications, we decided to explore the mechanisms of action of DF in a hepatic endothelial in vitromodel. OBJECTIVES: To investigate the interaction of DF with a hepatic endothelial cell line from human origin (SK-HEP-1), the mechanisms involved in its traffic and its potential protective effect on fludarabine induced apoptotic mechanisms. METHODS: SK-HEP-1 cells were exposed to DF (20µg/ml), previously labelled with ULYSIS® Nucleic Acid Labeling Kit, for up to 24 hours. Confocal microscopy (CM, Leica TCS SP5) was used to localize DF into the different cell compartments. Additional experiments were performed to assess colocalization of DF with different endocytosis pathways, by using specific antibodies. MTT assay to measure cell viability was performed in SK-HEP-1 cells after incubation with DF at different concentrations (10 to 200µg/mL, for 24h) followed by fludarabine exposure (at 20µg/mL, for 24h). RESULTS: CM analysis revealed a significant interaction of DF with endothelial cell membranes followed by internalization and redistribution to the cytoplasm. Mechanisms involved seem to be dependent on endosomes and cytoskeletal assembly. DF did not reach the cell nucleus even after 24h of exposure. In addition, MTT assay demonstrated the protective effect of DF (at concentrations >20µg/mL) on the fludarabine damage on endothelial cells. CONCLUSIONS: Our studies show that DF interacts with endothelial cell membranes, becoming internalized and redistributed into the endothelial cell cytoplasm without evidence in the nucleus. Moreover, DF protects hepatic endothelial cells from the toxic effect of fludarabine. Our findings may 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. Partially supported by grant SAF2011-28214 (Spanish MINECO and FEDER). Disclosures Diaz-Ricart: Gentium / Jazz Pharmaceuticals: Research Funding. Palomo:Gentium / Jazz Pharmaceuticals: Research Funding. Mir:Gentium / Jazz Pharmaceuticals: Research Funding. Carreras:Gentium / Jazz Pharmaceuticals: Research Funding.

Cholinesterase inhibitors exert a protective effect on endothelial damage in Alzheimer disease patients

2005 ◽  
Vol 229-230 ◽  
pp. 211-213 ◽  
Author(s):  
Barbara Borroni ◽  
Chiara Agosti ◽  
Giuliana Martini ◽  
Roberta Volpi ◽  
Cristina Brambilla ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Protective Effect ◽  
Cholinesterase Inhibitors ◽  
Endothelial Damage

Effect of Superoxide Dismutase on Endothelium-Dependent Relaxation of Aorta from Endotoxin-Treated Rabbits

1994 ◽  
Vol 22 (2) ◽  
pp. 113-120 ◽  
Author(s):  
H Yaku ◽  
K Mikawa ◽  
K Nishina ◽  
N Maekawa ◽  
H Obara
Keyword(s):  
Superoxide Dismutase ◽  
Protective Effect ◽  
Treated Group ◽  
Endothelial Damage ◽  
Histological Studies ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Endothelium Dependent Relaxation

To assess the protective effect of superoxide dismutase (SOD) on the endothelium of aorta in endotoxaemia, we investigated the production of endothelium-derived relaxing factor in aorta obtained from endotoxin-treated rabbits concomitantly receiving SOD or not. Thirty-two male Japanese white rabbits were randomly divided into four groups ( n = 8 for each group): one group receiving saline as a placebo, a second receiving 5 mg/kg endotoxin intravenously, a third receiving 5 mg/kg endotoxin intravenously plus SOD, and a fourth receiving SOD alone. SOD was injected intravenously at a dose of 10 000 U/kg before the endotoxin and was infused continuously at a rate of 15 000 units/kg/h throughout the experiment. The tension of the aorta was recorded in vitro 6 h after the start of in vivo treatment with endotoxin or saline. In the aorta of rabbits receiving endotoxin alone, acetylcholine-induced relaxation was reduced by 50%. The SOD fully restored the reduction of acetylcholine-induced relaxation by endotoxin. Histological studies using photomicroscopy revealed endothelial damage in the endotoxin-treated aorta, which was attenuated in the SOD-treated group. These data suggest that intravenous SOD may be an effective treatment for unstable haemodynamics in endotoxaemia.

scholarly journals A Novel Endothelial Damage Inhibitor Reduces Oxidative Stress and Improves Cellular Integrity in Radial Artery Grafts for Coronary Artery Bypass

2021 ◽  
Vol 8 ◽  
Author(s):  
Thomas Aschacher ◽  
Ulrike Baranyi ◽  
Olivia Aschacher ◽  
Eva Eichmair ◽  
Barbara Messner ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Protective Effect ◽  
Coronary Artery Bypass ◽  
Radial Artery ◽  
Ex Vivo ◽  
Artery Bypass ◽  
Endothelial Damage ◽  
Protective Function ◽  
Graft Disease

The radial artery (RA) is a frequently used conduit in coronary artery bypass grafting (CABG). Endothelial injury incurred during graft harvesting promotes oxidative damage, which leads to graft disease and graft failure. We evaluated the protective effect of DuraGraft®, an endothelial damage inhibitor (EDI), on RA grafts. We further compared the protective effect of the EDI between RA grafts and saphenous vein grafts (SVG). Samples of RA (n = 10) and SVG (n = 13) from 23 patients undergoing CABG were flushed and preserved with either EDI or heparinized Ringer's lactate solution (RL). The effect of EDI vs. RL on endothelial damage was evaluated ex vivo and in vitro using histological analysis, immunofluorescence staining, Western blot, and scanning electron microscopy. EDI-treated RA grafts showed a significant reduction of endothelial and sub-endothelial damage. Lower level of reactive oxygen species (ROS) after EDI treatment was correlated with a reduction of hypoxic damage (eNOS and Caveolin-1) and significant increase of oxidation-reduction potential. Additionally, an increased expression of TGFβ, PDGFα/β, and HO-1 which are indicative for vascular protective function were observed after EDI exposure. EDI treatment preserves functionality and integrity of endothelial and intimal cells. Therefore, EDI may have the potential to reduce the occurrence of graft disease and failure in RA grafts in patients undergoing CABG.

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