Download PDF
Semin Thromb Hemost 2015; 41(06): 629-643
DOI: 10.1055/s-0035-1556728
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Interplay of Inflammation and Endothelial Dysfunction in Bone Marrow Transplantation: Focus on Hepatic Veno-Occlusive Disease

Anne-Clémence Vion
1   Vascular Biology Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom
,
Pierre-Emmanuel Rautou
2   Paris Cardiovascular Research Center, Université Paris Descartes, Paris, France
3   DHU UNITY, Service d'Hépatologie, Hôpital Beaujon APHP, Clichy, France
,
François Durand
3   DHU UNITY, Service d'Hépatologie, Hôpital Beaujon APHP, Clichy, France
,
Chantal M. Boulanger
2   Paris Cardiovascular Research Center, Université Paris Descartes, Paris, France
,
Dominique C. Valla
3   DHU UNITY, Service d'Hépatologie, Hôpital Beaujon APHP, Clichy, France
› Author Affiliations
Further Information

Publication History

Publication Date:
25 August 2015 (online)

    Permissions and Reprints

Abstract

Endothelial cells are unique multifunctional cells with basal and inducible metabolic and synthetic functions. Various stimuli can induce physiological or pathological changes in endothelial cell biology. Hematopoietic stem cell transplantation (HSCT) requires high-dose irradiation and/or chemotherapy and is associated with increased risk of bacterial infections and immune reactions. These factors can affect endothelial cells. This review provides an overview of the effects of HSCT on endothelial cells, based on findings observed in cultured cells as well as in patients. We first describe to what extent irradiation and chemotherapy constitute direct and indirect triggers for endothelial cell activation and injury. Then, we highlight the role of the endothelium in several complications of HSCT, including capillary leak syndrome, engraftment syndrome, transplant-associated microangiopathy, graft-versus-host disease, and diffuse alveolar hemorrhages. We also analyze in detail available data on sinusoidal obstruction syndrome, previously known as veno-occlusive disease of the liver, where liver sinusoidal endothelial cells are first injured and eventually lead to sinusoid occlusion and liver cell damage. Finally, we open the question of the possible contribution of endothelial damage to cardiovascular events occurring long after HSCT.

Keywords

endothelial cells - endothelial damage - sinusoidal obstruction syndrome - hematopoietic stem cell transplant

Financial Support

This work was supported by the Agence Nationale pour la Recherche (ANR-12-EMMA-0012–03). A.-C. V. is supported by a fellowship from the BIRAX Regenerative Medicine initiative.


 

  • References

  • 1 Cines DB, Pollak ES, Buck CA , et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998; 91 (10) 3527-3561
    PubMedGoogle Scholar
  • 2 Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation 2007; 115 (10) 1285-1295
    CrossrefPubMedGoogle Scholar
  • 3 Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation 2004; 109 (23) (Suppl. 01) III27-III32
    CrossrefPubMedGoogle Scholar
  • 4 Pearson JD. Endothelial cell function and thrombosis. Best Pract Res Clin Haematol 1999; 12 (3) 329-341
    CrossrefPubMedGoogle Scholar
  • 5 Dudley AC. Tumor endothelial cells. Cold Spring Harb Perspect Med 2012; 2 (3) a006536
    PubMedGoogle Scholar
  • 6 Richard S, Seigneur M, Blann A , et al. Vascular endothelial lesion in patients undergoing bone marrow transplantation. Bone Marrow Transplant 1996; 18 (5) 955-959
    PubMedGoogle Scholar
  • 7 Palomo M, Diaz-Ricart M, Carbo C , et al. Endothelial dysfunction after hematopoietic stem cell transplantation: role of the conditioning regimen and the type of transplantation. Biol Blood Marrow Transplant 2010; 16 (7) 985-993
    CrossrefPubMedGoogle Scholar
  • 8 Sabatier F, Camoin-Jau L, Anfosso F, Sampol J, Dignat-George F. Circulating endothelial cells, microparticles and progenitors: key players towards the definition of vascular competence. J Cell Mol Med 2009; 13 (3) 454-471
    CrossrefPubMedGoogle Scholar
  • 9 Szmigielska-Kaplon A, Krawczynska A, Czemerska M , et al. The kinetics and apoptotic profile of circulating endothelial cells in autologous hematopoietic stem cell transplantation in patients with lymphoproliferative disorders. Ann Hematol 2013; 92 (9) 1255-1262
    CrossrefPubMedGoogle Scholar
  • 10 Pytlík R, Kideryová L, Benesová K , et al. Circulating endothelial precursor cells (EPC) in patients undergoing allogeneic haematopoietic progenitor cell transplantation. Folia Biol (Praha) 2010; 56 (1) 32-35
    PubMedGoogle Scholar
  • 11 Mause SF, Weber C. Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res 2010; 107 (9) 1047-1057
    CrossrefPubMedGoogle Scholar
  • 12 Nomura S, Ishii K, Inami N , et al. Evaluation of angiopoietins and cell-derived microparticles after stem cell transplantation. Biol Blood Marrow Transplant 2008; 14 (7) 766-774
    CrossrefPubMedGoogle Scholar
  • 13 Pihusch V, Rank A, Steber R , et al. Endothelial cell-derived microparticles in allogeneic hematopoietic stem cell recipients. Transplantation 2006; 81 (10) 1405-1409
    CrossrefPubMedGoogle Scholar
  • 14 Rautou PE, Vion AC, Amabile N , et al. Microparticles, vascular function, and atherothrombosis. Circ Res 2011; 109 (5) 593-606
    CrossrefPubMedGoogle Scholar
  • 15 Eissner G, Kohlhuber F, Grell M , et al. Critical involvement of transmembrane tumor necrosis factor-alpha in endothelial programmed cell death mediated by ionizing radiation and bacterial endotoxin. Blood 1995; 86 (11) 4184-4193
    PubMedGoogle Scholar
  • 16 Hong CW, Kim YM, Pyo H , et al. Involvement of inducible nitric oxide synthase in radiation-induced vascular endothelial damage. J Radiat Res (Tokyo) 2013; 54 (6) 1036-1042
    CrossrefPubMedGoogle Scholar
  • 17 Zeng L, Ding S, Yan Z , et al. Irradiation induces homing of donor endothelial progenitor cells in allogeneic hematopoietic stem cell transplantation. Int J Hematol 2012; 95 (2) 189-197
    CrossrefPubMedGoogle Scholar
  • 18 Panés J, Anderson DC, Miyasaka M, Granger DN. Role of leukocyte-endothelial cell adhesion in radiation-induced microvascular dysfunction in rats. Gastroenterology 1995; 108 (6) 1761-1769
    CrossrefPubMedGoogle Scholar
  • 19 Zeng L, Yan Z, Ding S, Xu K, Wang L. Endothelial injury, an intriguing effect of methotrexate and cyclophosphamide during hematopoietic stem cell transplantation in mice. Transplant Proc 2008; 40 (8) 2670-2673
    CrossrefPubMedGoogle Scholar
  • 20 Zeng L, Jia L, Xu S, Yan Z, Ding S, Xu K. Vascular endothelium changes after conditioning in hematopoietic stem cell transplantation: role of cyclophosphamide and busulfan. Transplant Proc 2010; 42 (7) 2720-2724
    CrossrefPubMedGoogle Scholar
  • 21 Zoja C, Furci L, Ghilardi F, Zilio P, Benigni A, Remuzzi G. Cyclosporin-induced endothelial cell injury. Lab Invest 1986; 55 (4) 455-462
    PubMedGoogle Scholar
  • 22 Carmona A, Díaz-Ricart M, Palomo M , et al. Distinct deleterious effects of cyclosporine and tacrolimus and combined tacrolimus-sirolimus on endothelial cells: protective effect of defibrotide. Biol Blood Marrow Transplant 2013; 19 (10) 1439-1445
    CrossrefPubMedGoogle Scholar
  • 23 Fusté B, Mazzara R, Escolar G, Merino A, Ordinas A, Díaz-Ricart M. Granulocyte colony-stimulating factor increases expression of adhesion receptors on endothelial cells through activation of p38 MAPK. Haematologica 2004; 89 (5) 578-585
    PubMedGoogle Scholar
  • 24 Levy O, Teixeira-Pinto A, White ML , et al. Endotoxemia and elevation of lipopolysaccharide-binding protein after hematopoietic stem cell transplantation. Pediatr Infect Dis J 2003; 22 (11) 978-981
    CrossrefPubMedGoogle Scholar
  • 25 Mantovani A, Bussolino F, Dejana E. Cytokine regulation of endothelial cell function. FASEB J 1992; 6 (8) 2591-2599
    PubMedGoogle Scholar
  • 26 van Gils JM, Zwaginga JJ, Hordijk PL. Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases. J Leukoc Biol 2009; 85 (2) 195-204
    CrossrefPubMedGoogle Scholar
  • 27 Palomo M, Diaz-Ricart M, Carbo C , et al. The release of soluble factors contributing to endothelial activation and damage after hematopoietic stem cell transplantation is not limited to the allogeneic setting and involves several pathogenic mechanisms. Biol Blood Marrow Transplant 2009; 15 (5) 537-546
    CrossrefPubMedGoogle Scholar
  • 28 Mehta D, Malik AB. Signaling mechanisms regulating endothelial permeability. Physiol Rev 2006; 86 (1) 279-367
    CrossrefPubMedGoogle Scholar
  • 29 Mallat Z, Tedgui A. Apoptosis in the vasculature: mechanisms and functional importance. Br J Pharmacol 2000; 130 (5) 947-962
    CrossrefPubMedGoogle Scholar
  • 30 Ganster A, Brucker I, Holler E , et al. In vitro monitoring of endothelial complications following hematopoietic allogeneic stem cell transplantation. Bone Marrow Transplant 2004; 33 (3) 355-357
    CrossrefPubMedGoogle Scholar
  • 31 Eissner G, Multhoff G, Holler E. Influence of bacterial endotoxin on the allogenicity of human endothelial cells. Bone Marrow Transplant 1998; 21 (12) 1286-1288
    CrossrefPubMedGoogle Scholar
  • 32 Eissner G, Multhoff G, Gerbitz A , et al. Fludarabine induces apoptosis, activation, and allogenicity in human endothelial and epithelial cells: protective effect of defibrotide. Blood 2002; 100 (1) 334-340
    CrossrefPubMedGoogle Scholar
  • 33 Nürnberger W, Willers R, Burdach S, Göbel U. Risk factors for capillary leakage syndrome after bone marrow transplantation. Ann Hematol 1997; 74 (5) 221-224
    CrossrefPubMedGoogle Scholar
  • 34 Lesterhuis WJ, Rennings AJ, Leenders WP , et al. Vascular endothelial growth factor in systemic capillary leak syndrome. Am J Med 2009; 122 (6) e5-e7
    CrossrefPubMedGoogle Scholar
  • 35 Assaly R, Olson D, Hammersley J , et al. Initial evidence of endothelial cell apoptosis as a mechanism of systemic capillary leak syndrome. Chest 2001; 120 (4) 1301-1308
    CrossrefPubMedGoogle Scholar
  • 36 Holler E, Kolb HJ, Möller A , et al. Increased serum levels of tumor necrosis factor alpha precede major complications of bone marrow transplantation. Blood 1990; 75 (4) 1011-1016
    PubMedGoogle Scholar
  • 37 Salat C, Holler E, Kolb HJ , et al. The relevance of plasminogen activator inhibitor 1 (PAI-1) as a marker for the diagnosis of hepatic veno-occlusive disease in patients after bone marrow transplantation. Leuk Lymphoma 1999; 33 (1-2) 25-32
    CrossrefPubMedGoogle Scholar
  • 38 Nürnberger W, Michelmann I, Burdach S, Göbel U. Endothelial dysfunction after bone marrow transplantation: increase of soluble thrombomodulin and PAI-1 in patients with multiple transplant-related complications. Ann Hematol 1998; 76 (2) 61-65
    CrossrefPubMedGoogle Scholar
  • 39 Dowden AM, Rullo OJ, Aziz N, Fasano MB, Chatila T, Ballas ZK. Idiopathic systemic capillary leak syndrome: novel therapy for acute attacks. J Allergy Clin Immunol 2009; 124 (5) 1111-1113
    CrossrefPubMedGoogle Scholar
  • 40 Cicardi M, Gardinali M, Bisiani G, Rosti A, Allavena P, Agostoni A. The systemic capillary leak syndrome: appearance of interleukin-2-receptor-positive cells during attacks. Ann Intern Med 1990; 113 (6) 475-477
    CrossrefPubMedGoogle Scholar
  • 41 Spitzer TR. Engraftment syndrome following hematopoietic stem cell transplantation. Bone Marrow Transplant 2001; 27 (9) 893-898
    CrossrefPubMedGoogle Scholar
  • 42 Gorak E, Geller N, Srinivasan R , et al. Engraftment syndrome after nonmyeloablative allogeneic hematopoietic stem cell transplantation: incidence and effects on survival. Biol Blood Marrow Transplant 2005; 11 (7) 542-550
    CrossrefPubMedGoogle Scholar
  • 43 Maiolino A, Biasoli I, Lima J, Portugal AC, Pulcheri W, Nucci M. Engraftment syndrome following autologous hematopoietic stem cell transplantation: definition of diagnostic criteria. Bone Marrow Transplant 2003; 31 (5) 393-397
    CrossrefPubMedGoogle Scholar
  • 44 Pidala J. Graft-vs-host disease following allogeneic hematopoietic cell transplantation. Cancer Contr 2011; 18 (4) 268-276
    PubMedGoogle Scholar
  • 45 Bolaños-Meade J, Ioffe O, Hey JC, Vogelsang GB, Akpek G. Lymphocytic pneumonitis as the manifestation of acute graft-versus-host disease of the lung. Am J Hematol 2005; 79 (2) 132-135
    CrossrefPubMedGoogle Scholar
  • 46 Ratanatharathorn V, Ayash L, Lazarus HM, Fu J, Uberti JP. Chronic graft-versus-host disease: clinical manifestation and therapy. Bone Marrow Transplant 2001; 28 (2) 121-129
    CrossrefPubMedGoogle Scholar
  • 47 Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet 2009; 373 (9674) 1550-1561
    CrossrefPubMedGoogle Scholar
  • 48 Dumler JS, Beschorner WE, Farmer ER, Di Gennaro KA, Saral R, Santos GW. Endothelial-cell injury in cutaneous acute graft-versus-host disease. Am J Pathol 1989; 135 (6) 1097-1103
    PubMedGoogle Scholar
  • 49 Strasser SI, Shulman HM, Flowers ME , et al. Chronic graft-versus-host disease of the liver: presentation as an acute hepatitis. Hepatology 2000; 32 (6) 1265-1271
    CrossrefPubMedGoogle Scholar
  • 50 Ferrara JL. Pathogenesis of acute graft-versus-host disease: cytokines and cellular effectors. J Hematother Stem Cell Res 2000; 9 (3) 299-306
    CrossrefPubMedGoogle Scholar
  • 51 Nomura S, Ishii K, Inami N , et al. Role of soluble tumor necrosis factor-related apoptosis-inducing ligand concentrations after stem cell transplantation. Transpl Immunol 2007; 18 (2) 115-121
    CrossrefPubMedGoogle Scholar
  • 52 Madge LA, Pober JS. TNF signaling in vascular endothelial cells. Exp Mol Pathol 2001; 70 (3) 317-325
    CrossrefPubMedGoogle Scholar
  • 53 Matsuda Y, Hara J, Osugi Y , et al. Serum levels of soluble adhesion molecules in stem cell transplantation-related complications. Bone Marrow Transplant 2001; 27 (9) 977-982
    CrossrefPubMedGoogle Scholar
  • 54 Salat C, Holler E, Kolb HJ, Pihusch R, Reinhardt B, Hiller E. Endothelial cell markers in bone marrow transplant recipients with and without acute graft-versus-host disease. Bone Marrow Transplant 1997; 19 (9) 909-914
    CrossrefPubMedGoogle Scholar
  • 55 Byrne AM, Bouchier-Hayes DJ, Harmey JH. Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF). J Cell Mol Med 2005; 9 (4) 777-794
    CrossrefPubMedGoogle Scholar
  • 56 Augustin HG, Koh GY, Thurston G, Alitalo K. Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system. Nat Rev Mol Cell Biol 2009; 10 (3) 165-177
    CrossrefPubMedGoogle Scholar
  • 57 Lunn RA, Sumar N, Bansal AS, Treleaven J. Cytokine profiles in stem cell transplantation: possible use as a predictor of graft-versus-host disease. Hematology 2005; 10 (2) 107-114
    CrossrefPubMedGoogle Scholar
  • 58 Moiseev IS, Lapin SV, Surkova EA, Lerner MY, Vavilov VN, Afanasyev BV. Level of vascular endothelial growth factor predicts both relapse and nonrelapse mortality after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2013; 19 (12) 1677-1682
    CrossrefPubMedGoogle Scholar
  • 59 Luft T, Dietrich S, Falk C , et al. Steroid-refractory GVHD: T-cell attack within a vulnerable endothelial system. Blood 2011; 118 (6) 1685-1692
    CrossrefPubMedGoogle Scholar
  • 60 Ruutu T, Barosi G, Benjamin RJ , et al; European Group for Blood and Marrow Transplantation; European LeukemiaNet. Diagnostic criteria for hematopoietic stem cell transplant-associated microangiopathy: results of a consensus process by an International Working Group. Haematologica 2007; 92 (1) 95-100
    CrossrefPubMedGoogle Scholar
  • 61 Inamoto Y, Ito M, Suzuki R , et al; Nagoya Blood and Marrow Transplantation Group. Clinicopathological manifestations and treatment of intestinal transplant-associated microangiopathy. Bone Marrow Transplant 2009; 44 (1) 43-49
    CrossrefPubMedGoogle Scholar
  • 62 Ruutu T, Hermans J, Niederwieser D , et al; EBMT Chronic Leukaemia Working Party. Thrombotic thrombocytopenic purpura after allogeneic stem cell transplantation: a survey of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 2002; 118 (4) 1112-1119
    CrossrefPubMedGoogle Scholar
  • 63 Shimoni A, Yeshurun M, Hardan I, Avigdor A, Ben-Bassat I, Nagler A. Thrombotic microangiopathy after allogeneic stem cell transplantation in the era of reduced-intensity conditioning: The incidence is not reduced. Biol Blood Marrow Transplant 2004; 10 (7) 484-493
    CrossrefPubMedGoogle Scholar
  • 64 Tsai HM, Lian EC. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 1998; 339 (22) 1585-1594
    CrossrefPubMedGoogle Scholar
  • 65 van der Plas RM, Schiphorst ME, Huizinga EG , et al. von Willebrand factor proteolysis is deficient in classic, but not in bone marrow transplantation-associated, thrombotic thrombocytopenic purpura. Blood 1999; 93 (11) 3798-3802
    PubMedGoogle Scholar
  • 66 Schriber JR, Herzig GP. Transplantation-associated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Semin Hematol 1997; 34 (2) 126-133
    PubMedGoogle Scholar
  • 67 Cohen H, Bull HA, Seddon A , et al. Vascular endothelial cell function and ultrastructure in thrombotic microangiopathy following allogeneic bone marrow transplantation. Eur J Haematol 1989; 43 (3) 207-214
    PubMedGoogle Scholar
  • 68 Jodele S, Licht C, Goebel J , et al. Abnormalities in the alternative pathway of complement in children with hematopoietic stem cell transplant-associated thrombotic microangiopathy. Blood 2013; 122 (12) 2003-2007
    CrossrefPubMedGoogle Scholar
  • 69 Zeigler ZR, Rosenfeld CS, Andrews III DF , et al. Plasma von Willebrand Factor Antigen (vWF:AG) and thrombomodulin (TM) levels in Adult Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndromes (TTP/HUS) and bone marrow transplant-associated thrombotic microangiopathy (BMT-TM). Am J Hematol 1996; 53 (4) 213-220
    CrossrefPubMedGoogle Scholar
  • 70 Anthony MT, Zeigler ZR, Lister J , et al. Plasminogen activator inhibitor (PAI-1) antigen levels in primary TTP and secondary TTP post-bone marrow transplantation. Am J Hematol 1998; 59 (1) 9-14
    CrossrefPubMedGoogle Scholar
  • 71 Elliott MA, Nichols Jr WL, Plumhoff EA , et al. Posttransplantation thrombotic thrombocytopenic purpura: a single-center experience and a contemporary review. Mayo Clin Proc 2003; 78 (4) 421-430
    CrossrefPubMedGoogle Scholar
  • 72 Laskin BL, Maisel J, Goebel J , et al. Renal arteriolar C4d deposition: a novel characteristic of hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Transplantation 2013; 96 (2) 217-223
    CrossrefPubMedGoogle Scholar
  • 73 Fujino M, Kim Y, Ito M. Intestinal thrombotic microangiopathy induced by FK506 in rats. Bone Marrow Transplant 2007; 39 (6) 367-372
    CrossrefPubMedGoogle Scholar
  • 74 Mitra D, Jaffe EA, Weksler B, Hajjar KA, Soderland C, Laurence J. Thrombotic thrombocytopenic purpura and sporadic hemolytic-uremic syndrome plasmas induce apoptosis in restricted lineages of human microvascular endothelial cells. Blood 1997; 89 (4) 1224-1234
    PubMedGoogle Scholar
  • 75 Mitra D, Kim J, MacLow C, Karsan A, Laurence J. Role of caspases 1 and 3 and Bcl-2-related molecules in endothelial cell apoptosis associated with thrombotic microangiopathies. Am J Hematol 1998; 59 (4) 279-287
    CrossrefPubMedGoogle Scholar
  • 76 Lee JL, Gooley T, Bensinger W, Schiffman K, McDonald GB. Veno-occlusive disease of the liver after busulfan, melphalan, and thiotepa conditioning therapy: incidence, risk factors, and outcome. Biol Blood Marrow Transplant 1999; 5 (5) 306-315
    CrossrefPubMedGoogle Scholar
  • 77 McDonald GB, Hinds MS, Fisher LD , et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med 1993; 118 (4) 255-267
    CrossrefPubMedGoogle Scholar
  • 78 Carreras E, Bertz H, Arcese W , et al; European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party. Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: a prospective cohort study of the European Group for Blood and Marrow Transplantation. Blood 1998; 92 (10) 3599-3604
    PubMedGoogle Scholar
  • 79 DeLeve LD, Valla DC, Garcia-Tsao G ; American Association for the Study Liver Diseases. Vascular disorders of the liver. Hepatology 2009; 49 (5) 1729-1764
    CrossrefPubMedGoogle Scholar
  • 80 Girinsky T, Benhamou E, Bourhis JH , et al. Prospective randomized comparison of single-dose versus hyperfractionated total-body irradiation in patients with hematologic malignancies. J Clin Oncol 2000; 18 (5) 981-986
    PubMedGoogle Scholar
  • 81 Shulman HM, Fisher LB, Schoch HG, Henne KW, McDonald GB. Veno-occlusive disease of the liver after marrow transplantation: histological correlates of clinical signs and symptoms. Hepatology 1994; 19 (5) 1171-1181
    CrossrefPubMedGoogle Scholar
  • 82 Sato Y, Asada Y, Hara S , et al. Hepatic stellate cells (Ito cells) in veno-occlusive disease of the liver after allogeneic bone marrow transplantation. Histopathology 1999; 34 (1) 66-70
    CrossrefPubMedGoogle Scholar
  • 83 Shulman HM, McDonald GB, Matthews D , et al. An analysis of hepatic venocclusive disease and centrilobular hepatic degeneration following bone marrow transplantation. Gastroenterology 1980; 79 (6) 1178-1191
    PubMedGoogle Scholar
  • 84 Shulman HM, Gown AM, Nugent DJ. Hepatic veno-occlusive disease after bone marrow transplantation. Immunohistochemical identification of the material within occluded central venules. Am J Pathol 1987; 127 (3) 549-558
    PubMedGoogle Scholar
  • 85 Korte W. Veno-occlusive disease of the liver after bone marrow transplantation: is hypercoagulability really part of the problem?. Blood Coagul Fibrinolysis 1997; 8 (7) 367-381
    CrossrefPubMedGoogle Scholar
  • 86 DeLeve LD, McCuskey RS, Wang X , et al. Characterization of a reproducible rat model of hepatic veno-occlusive disease. Hepatology 1999; 29 (6) 1779-1791
    CrossrefPubMedGoogle Scholar
  • 87 Cutler C, Kim HT, Ayanian S , et al. Prediction of veno-occlusive disease using biomarkers of endothelial injury. Biol Blood Marrow Transplant 2010; 16 (8) 1180-1185
    CrossrefPubMedGoogle Scholar
  • 88 Heloterä H, Alitalo K. The VEGF family, the inside story. Cell 2007; 130 (4) 591-592
    CrossrefPubMedGoogle Scholar
  • 89 DeLeve LD, Wang X, Kuhlenkamp JF, Kaplowitz N. Toxicity of azathioprine and monocrotaline in murine sinusoidal endothelial cells and hepatocytes: the role of glutathione and relevance to hepatic venoocclusive disease. Hepatology 1996; 23 (3) 589-599
    CrossrefPubMedGoogle Scholar
  • 90 Wolf CR, Moll E, Friedberg T , et al. Characterization, localization and regulation of a novel phenobarbital-inducible form of cytochrome P450, compared with three further P450-isoenzymes, NADPH P450-reductase, glutathione transferases and microsomal epoxide hydrolase. Carcinogenesis 1984; 5 (8) 993-1001
    CrossrefPubMedGoogle Scholar
  • 91 DeLeve LD. Cellular target of cyclophosphamide toxicity in the murine liver: role of glutathione and site of metabolic activation. Hepatology 1996; 24 (4) 830-837
    CrossrefPubMedGoogle Scholar
  • 92 DeLeve LD, Wang X. Role of oxidative stress and glutathione in busulfan toxicity in cultured murine hepatocytes. Pharmacology 2000; 60 (3) 143-154
    CrossrefPubMedGoogle Scholar
  • 93 Wang X, Kanel GC, DeLeve LD. Support of sinusoidal endothelial cell glutathione prevents hepatic veno-occlusive disease in the rat. Hepatology 2000; 31 (2) 428-434
    CrossrefPubMedGoogle Scholar
  • 94 Barkholt L, Remberger M, Hassan Z , et al. A prospective randomized study using N-acetyl-L-cysteine for early liver toxicity after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2008; 41 (9) 785-790
    CrossrefPubMedGoogle Scholar
  • 95 Kachel DL, Martin II WJ. Cyclophosphamide-induced lung toxicity: mechanism of endothelial cell injury. J Pharmacol Exp Ther 1994; 268 (1) 42-46
    PubMedGoogle Scholar
  • 96 DeLeve LD, Wang X, Kanel GC , et al. Decreased hepatic nitric oxide production contributes to the development of rat sinusoidal obstruction syndrome. Hepatology 2003; 38 (4) 900-908
    CrossrefPubMedGoogle Scholar
  • 97 Deleve LD, Wang X, Tsai J, Kanel G, Strasberg S, Tokes ZA. Sinusoidal obstruction syndrome (veno-occlusive disease) in the rat is prevented by matrix metalloproteinase inhibition. Gastroenterology 2003; 125 (3) 882-890
    CrossrefPubMedGoogle Scholar
  • 98 Upadhya GA, Strasberg SM. Glutathione, lactobionate, and histidine: cryptic inhibitors of matrix metalloproteinases contained in University of Wisconsin and histidine/tryptophan/ketoglutarate liver preservation solutions. Hepatology 2000; 31 (5) 1115-1122
    CrossrefPubMedGoogle Scholar
  • 99 Nakamura K, Hatano E, Narita M , et al. Sorafenib attenuates monocrotaline-induced sinusoidal obstruction syndrome in rats through suppression of JNK and MMP-9. J Hepatol 2012; 57 (5) 1037-1043
    CrossrefPubMedGoogle Scholar
  • 100 Grabham P, Sharma P. Acute effects of ionizing radiation on human endothelial barrier function. J Radiat Res (Tokyo) 2014; 55 (Suppl. 01) i97-i98
    CrossrefPubMedGoogle Scholar
  • 101 Harb R, Xie G, Lutzko C , et al. Bone marrow progenitor cells repair rat hepatic sinusoidal endothelial cells after liver injury. Gastroenterology 2009; 137 (2) 704-712
    CrossrefPubMedGoogle Scholar
  • 102 Wang L, Wang X, Wang L , et al. Hepatic vascular endothelial growth factor regulates recruitment of rat liver sinusoidal endothelial cell progenitor cells. Gastroenterology 2012; 143 (6) 1555-1563.e2
    CrossrefPubMedGoogle Scholar
  • 103 Palmer KJ, Goa KL. Defibrotide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in vascular disorders. Drugs 1993; 45 (2) 259-294
    PubMedGoogle Scholar
  • 104 Masini E, Lupini M, Mugnai L, Raspanti S, Mannaioni PF. Polydeoxyribonucleotides and nitric oxide release from guinea-pig hearts during ischaemia and reperfusion. Br J Pharmacol 1995; 115 (4) 629-635
    CrossrefPubMedGoogle Scholar
  • 105 Berti F, Rossoni G, Biasi G, Buschi A, Mandelli V, Tondo C. Defibrotide, by enhancing prostacyclin generation, prevents endothelin-1 induced contraction in human saphenous veins. Prostaglandins 1990; 40 (4) 337-350
    CrossrefPubMedGoogle Scholar
  • 106 Klöcking HP. Acute t-PA release by defibrotide. Thromb Res 1992; 66 (6) 779-785
    CrossrefPubMedGoogle Scholar
  • 107 Falanga A, Vignoli A, Marchetti M, Barbui T. Defibrotide reduces procoagulant activity and increases fibrinolytic properties of endothelial cells. Leukemia 2003; 17 (8) 1636-1642
    CrossrefPubMedGoogle Scholar
  • 108 San T, Moini H, Emerk K, Bilsel S. Protective effect of defibrotide on perfusion induced endothelial damage. Thromb Res 2000; 99 (4) 335-341
    CrossrefPubMedGoogle Scholar
  • 109 Pellegatta F, Lu Y, Radaelli A , et al. Drug-induced in vitro inhibition of neutrophil-endothelial cell adhesion. Br J Pharmacol 1996; 118 (3) 471-476
    CrossrefPubMedGoogle Scholar
  • 110 Corbacioglu S, Cesaro S, Faraci M , et al. Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial. Lancet 2012; 379 (9823) 1301-1309
    CrossrefPubMedGoogle Scholar
  • 111 Chalandon Y, Roosnek E, Mermillod B , et al. Prevention of veno-occlusive disease with defibrotide after allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2004; 10 (5) 347-354
    CrossrefPubMedGoogle Scholar
  • 112 Dignan F, Gujral D, Ethell M , et al. Prophylactic defibrotide in allogeneic stem cell transplantation: minimal morbidity and zero mortality from veno-occlusive disease. Bone Marrow Transplant 2007; 40 (1) 79-82
    CrossrefPubMedGoogle Scholar
  • 113 Qureshi A, Marshall L, Lancaster D. Defibrotide in the prevention and treatment of veno-occlusive disease in autologous and allogeneic stem cell transplantation in children. Pediatr Blood Cancer 2008; 50 (4) 831-832
    CrossrefPubMedGoogle Scholar
  • 114 Richardson PG, Elias AD, Krishnan A , et al. Treatment of severe veno-occlusive disease with defibrotide: compassionate use results in response without significant toxicity in a high-risk population. Blood 1998; 92 (3) 737-744
    PubMedGoogle Scholar
  • 115 Chopra R, Eaton JD, Grassi A , et al. Defibrotide for the treatment of hepatic veno-occlusive disease: results of the European compassionate-use study. Br J Haematol 2000; 111 (4) 1122-1129
    CrossrefPubMedGoogle Scholar
  • 116 Richardson PG, Murakami C, Jin Z , et al. Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure: response without significant toxicity in a high-risk population and factors predictive of outcome. Blood 2002; 100 (13) 4337-4343
    CrossrefPubMedGoogle Scholar
  • 117 Richardson PG, Soiffer RJ, Antin JH , et al. Defibrotide for the treatment of severe hepatic veno-occlusive disease and multiorgan failure after stem cell transplantation: a multicenter, randomized, dose-finding trial. Biol Blood Marrow Transplant 2010; 16 (7) 1005-1017
    CrossrefPubMedGoogle Scholar
  • 118 Bunte MC, Patnaik MM, Pritzker MR, Burns LJ. Pulmonary veno-occlusive disease following hematopoietic stem cell transplantation: a rare model of endothelial dysfunction. Bone Marrow Transplant 2008; 41 (8) 677-686
    CrossrefPubMedGoogle Scholar
  • 119 Afessa B, Tefferi A, Litzow MR, Krowka MJ, Wylam ME, Peters SG. Diffuse alveolar hemorrhage in hematopoietic stem cell transplant recipients. Am J Respir Crit Care Med 2002; 166 (5) 641-645
    CrossrefPubMedGoogle Scholar
  • 120 Majhail NS, Parks K, Defor TE, Weisdorf DJ. Diffuse alveolar hemorrhage and infection-associated alveolar hemorrhage following hematopoietic stem cell transplantation: related and high-risk clinical syndromes. Biol Blood Marrow Transplant 2006; 12 (10) 1038-1046
    CrossrefPubMedGoogle Scholar
  • 121 Park MS. Diffuse alveolar hemorrhage. Tuberc Respir Dis (Seoul) 2013; 74 (4) 151-162
    CrossrefPubMedGoogle Scholar
  • 122 Newsome BR, Morales JE. Diffuse alveolar hemorrhage. South Med J 2011; 104 (4) 269-274
    CrossrefPubMedGoogle Scholar
  • 123 Lantuéjoul S, Sheppard MN, Corrin B, Burke MM, Nicholson AG. Pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis: a clinicopathologic study of 35 cases. Am J Surg Pathol 2006; 30 (7) 850-857
    CrossrefPubMedGoogle Scholar
  • 124 Piguet PF, Grau GE, Collart MA, Vassalli P, Kapanci Y. Pneumopathies of the graft-versus-host reaction. Alveolitis associated with an increased level of tumor necrosis factor mRNA and chronic interstitial pneumonitis. Lab Invest 1989; 61 (1) 37-45
    PubMedGoogle Scholar
  • 125 Lalich JL, Johnson WD, Raczniak TJ, Shumaker RC. Fibrin thrombosis in monocrotaline pyrrole-induced cor pulmonale in rats. Arch Pathol Lab Med 1977; 101 (2) 69-73
    PubMedGoogle Scholar
  • 126 Gomez-Arroyo JG, Farkas L, Alhussaini AA , et al. The monocrotaline model of pulmonary hypertension in perspective. Am J Physiol Lung Cell Mol Physiol 2012; 302 (4) L363-L369
    CrossrefPubMedGoogle Scholar
  • 127 Lee J, Reich R, Xu F, Sehgal PB. Golgi, trafficking, and mitosis dysfunctions in pulmonary arterial endothelial cells exposed to monocrotaline pyrrole and NO scavenging. Am J Physiol Lung Cell Mol Physiol 2009; 297 (4) L715-L728
    CrossrefPubMedGoogle Scholar
  • 128 Sun X, Kumar S, Sharma S , et al. Endothelin-1 induces a glycolytic switch in pulmonary arterial endothelial cells via the mitochondrial translocation of endothelial nitric oxide synthase. Am J Respir Cell Mol Biol 2014; 50 (6) 1084-1095
    CrossrefPubMedGoogle Scholar
  • 129 Sehgal PB, Mukhopadhyay S. Dysfunctional intracellular trafficking in the pathobiology of pulmonary arterial hypertension. Am J Respir Cell Mol Biol 2007; 37 (1) 31-37
    CrossrefPubMedGoogle Scholar
  • 130 Huang J, Wolk JH, Gewitz MH, Mathew R. Progressive endothelial cell damage in an inflammatory model of pulmonary hypertension. Exp Lung Res 2010; 36 (1) 57-66
    CrossrefPubMedGoogle Scholar
  • 131 Yang YM, Lane KB, Sehgal PB. Subcellular mechanisms in pulmonary arterial hypertension: combinatorial modalities that inhibit anterograde trafficking and cause bone morphogenetic protein receptor type 2 mislocalization. Pulm Circ 2013; 3 (3) 533-550
    CrossrefPubMedGoogle Scholar
  • 132 Ramos M, Lamé MW, Segall HJ, Wilson DW. Monocrotaline pyrrole induces Smad nuclear accumulation and altered signaling expression in human pulmonary arterial endothelial cells. Vascul Pharmacol 2007; 46 (6) 439-448
    CrossrefPubMedGoogle Scholar
  • 133 Li L, Wei C, Kim IK, Janssen-Heininger Y, Gupta S. Inhibition of nuclear factor-κB in the lungs prevents monocrotaline-induced pulmonary hypertension in mice. Hypertension 2014; 63 (6) 1260-1269
    CrossrefPubMedGoogle Scholar
  • 134 Kothari SS, Jagia P, Gupta A, Singh N, Ray R. Images in cardiovascular medicine. Pulmonary capillary hemangiomatosis. Circulation 2009; 120 (4) 352-354
    CrossrefPubMedGoogle Scholar
  • 135 Assaad AM, Kawut SM, Arcasoy SM , et al. Platelet-derived growth factor is increased in pulmonary capillary hemangiomatosis. Chest 2007; 131 (3) 850-855
    CrossrefPubMedGoogle Scholar
  • 136 Armenian SH, Bhatia S. Cardiovascular disease after hematopoietic cell transplantation—lessons learned. Haematologica 2008; 93 (8) 1132-1136
    CrossrefPubMedGoogle Scholar
  • 137 Syrjala KL, Langer SL, Abrams JR, Storer BE, Martin PJ. Late effects of hematopoietic cell transplantation among 10-year adult survivors compared with case-matched controls. J Clin Oncol 2005; 23 (27) 6596-6606
    CrossrefPubMedGoogle Scholar
  • 138 Bhatia S, Ramsay NK, Steinbuch M , et al. Malignant neoplasms following bone marrow transplantation. Blood 1996; 87 (9) 3633-3639
    PubMedGoogle Scholar
  • 139 Socié G, Salooja N, Cohen A , et al; Late Effects Working Party of the European Study Group for Blood and Marrow Transplantation. Nonmalignant late effects after allogeneic stem cell transplantation. Blood 2003; 101 (9) 3373-3385
    CrossrefPubMedGoogle Scholar
  • 140 Tichelli A, Passweg J, Wójcik D , et al; EBMT Late Effects Working Party. Late cardiovascular events after allogeneic hematopoietic stem cell transplantation: a retrospective multicenter study of the Late Effects Working Party of the European Group for Blood and Marrow Transplantation. Haematologica 2008; 93 (8) 1203-1210
    CrossrefPubMedGoogle Scholar
  • 141 Abou-Mourad YR, Lau BC, Barnett MJ , et al. Long-term outcome after allo-SCT: close follow-up on a large cohort treated with myeloablative regimens. Bone Marrow Transplant 2010; 45 (2) 295-302
    CrossrefPubMedGoogle Scholar
  • 142 Bhatia S, Francisco L, Carter A , et al. Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study. Blood 2007; 110 (10) 3784-3792
    CrossrefPubMedGoogle Scholar
  • 143 Marsh G, Ehland J, Sefcik S, Youk A. Mortality and Population Data System. Pittsburgh, PA: University of Pittsburgh; 2000
    Google Scholar
  • 144 Lloyd-Jones DM, Wilson PW, Larson MG , et al. Framingham risk score and prediction of lifetime risk for coronary heart disease. Am J Cardiol 2004; 94 (1) 20-24
    CrossrefPubMedGoogle Scholar
  • 145 Taskinen M, Saarinen-Pihkala UM, Hovi L, Lipsanen-Nyman M. Impaired glucose tolerance and dyslipidaemia as late effects after bone-marrow transplantation in childhood. Lancet 2000; 356 (9234) 993-997
    CrossrefPubMedGoogle Scholar
  • 146 Baker KS, Ness KK, Steinberger J , et al. Diabetes, hypertension, and cardiovascular events in survivors of hematopoietic cell transplantation: a report from the bone marrow transplantation survivor study. Blood 2007; 109 (4) 1765-1772
    CrossrefPubMedGoogle Scholar
  • 147 Tichelli A, Bucher C, Rovó A , et al. Premature cardiovascular disease after allogeneic hematopoietic stem-cell transplantation. Blood 2007; 110 (9) 3463-3471
    CrossrefPubMedGoogle Scholar
  • 148 Couriel DR, Saliba R, Escalón MP , et al. Sirolimus in combination with tacrolimus and corticosteroids for the treatment of resistant chronic graft-versus-host disease. Br J Haematol 2005; 130 (3) 409-417
    CrossrefPubMedGoogle Scholar
  • 149 Goligorsky MS. Microvascular rarefaction: the decline and fall of blood vessels. Organogenesis 2010; 6 (1) 1-10
    CrossrefPubMedGoogle Scholar
  • 150 Haeusermann P, Kump E, Rovó A , et al. Partial reconstitution of cutaneous microvessels in long-term survivors after allogeneic bone marrow transplantation. Dermatology 2009; 219 (1) 32-41
    CrossrefPubMedGoogle Scholar
  • 151 Biedermann BC, Sahner S, Gregor M , et al. Endothelial injury mediated by cytotoxic T lymphocytes and loss of microvessels in chronic graft versus host disease. Lancet 2002; 359 (9323) 2078-2083
    CrossrefPubMedGoogle Scholar
  • 152 Espino G, Denney J, Furlong T, Fitzsimmons W, Nash RA. Assessment of myocardial hypertrophy by echocardiography in adult patients receiving tacrolimus or cyclosporine therapy for prevention of acute GVHD. Bone Marrow Transplant 2001; 28 (12) 1097-1103
    CrossrefPubMedGoogle Scholar
  • 153 Nakamura K, Hatano E, Miyagawa-Hayashino A , et al. Soluble thrombomodulin attenuates sinusoidal obstruction syndrome in rat through suppression of high mobility group box 1. Liver Int 2014; 34 (10) 1473-1487
    CrossrefPubMedGoogle Scholar
  • 154 Ueda N, Chihara D, Kohno A , et al. Predictive value of circulating angiopoietin-2 for endothelial damage-related complications in allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2014; 20 (9) 1335-1340
    CrossrefPubMedGoogle Scholar