Angiogenic factors are associated with development of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
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.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Di-Min
DM
Nie
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Qiu-Ling
QL
Wu
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Xia-Xia
XX
Zhu
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Ran
R
Zhang
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Peng
P
Zheng
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Jun
J
Fang
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Yong
Y
You
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Zhao-Dong
ZD
Zhong
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Ling-Hui
LH
Xia
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. meihongcncn@aliyun.com.
Mei
M
Hong
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D042683:Angiopoietin-1 / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology; D042702:Angiopoietin-2 / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D012189:Retrospective Studies; D015398:Signal Transduction; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology
C467630:ANGPT1 protein, human; C586513:ANGPT2 protein, human; D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
acute graft-versus-host disease; allogeneic hematopoietic stem cell transplantation; angiogenic factors; endothelial damage