Abstract
Acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the mechanisms of aGVHD are not well understood. We aim to investigate the roles of the three angiogenic factors: angiopoietin-1 (Ang-1), Ang-2 and vascular endothelial growth factor (VEGF) in the development of aGVHD. Twenty-one patients who underwent allo-HSCT were included in our study. The dynamic changes of Ang-1, Ang-2 and VEGF were monitored in patients before and after allo-HSCT. In vitro, endothelial cells (ECs) were treated with TNF-β in the presence or absence of Ang-1, and then the Ang-2 level in the cell culture medium and the tubule formation by ECs were evaluated. After allo-HSCT, Ang-1, Ang-2 and VEGF all exhibited significant variation, suggesting these factors might be involved in the endothelial damage in transplantation. Patients with aGVHD had lower Ang-1 level at day 7 but higher Ang-2 level at day 21 than those without aGVHD, implying that Ang-1 may play a protective role in early phase yet Ang-2 is a promotion factor to aGVHD. In vitro, TNF-β promoted the release of Ang-2 by ECs and impaired tubule formation of ECs, which were both weakened by Ang-1, suggesting that Ang-1 may play a protective role in aGVHD by influencing the secretion of Ang-2, consistent with our in vivo tests. It is concluded that monitoring changes of these factors following allo-HSCT might help to identify patients at a high risk for aGVHD.
Keywords:
acute graft-versus-host disease; allogeneic hematopoietic stem cell transplantation; angiogenic factors; endothelial damage.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Disease
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Adolescent
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Adult
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Angiogenesis Inducing Agents / immunology
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Angiogenesis Inducing Agents / metabolism
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Angiogenesis Inducing Agents / pharmacology
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Angiopoietin-1 / genetics*
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Angiopoietin-1 / immunology
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Angiopoietin-1 / pharmacology
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Angiopoietin-2 / genetics*
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Angiopoietin-2 / immunology
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Angiopoietin-2 / pharmacology
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Antineoplastic Agents / therapeutic use
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Female
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Gene Expression Regulation, Neoplastic
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Graft vs Host Disease / genetics
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Graft vs Host Disease / immunology
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Graft vs Host Disease / pathology
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Hematopoietic Stem Cell Transplantation*
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Human Umbilical Vein Endothelial Cells / cytology
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Human Umbilical Vein Endothelial Cells / drug effects
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Human Umbilical Vein Endothelial Cells / immunology
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Humans
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Leukemia, Myeloid / genetics*
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Leukemia, Myeloid / immunology
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Leukemia, Myeloid / pathology
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Leukemia, Myeloid / therapy
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Lymphoma, Non-Hodgkin / genetics*
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Lymphoma, Non-Hodgkin / immunology
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Lymphoma, Non-Hodgkin / pathology
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Lymphoma, Non-Hodgkin / therapy
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Male
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
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Retrospective Studies
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Signal Transduction
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Transplantation, Homologous
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Tumor Necrosis Factor-alpha / pharmacology
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / immunology
Substances
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ANGPT1 protein, human
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ANGPT2 protein, human
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Angiogenesis Inducing Agents
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Angiopoietin-1
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Angiopoietin-2
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Antineoplastic Agents
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Tumor Necrosis Factor-alpha
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VEGFA protein, human
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Vascular Endothelial Growth Factor A