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Angiogenic factors are associated with development of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

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Summary

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.

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Authors and Affiliations

  1. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Di-min Nie  (聂第敏), Qiu-ling Wu  (吴秋玲), Xia-xia Zhu  (朱夏夏), Ran Zhang  (张 然), Peng Zheng  (郑 鹏), Jun Fang  (方 俊), Yong You  (游 泳), Zhao-dong Zhong  (仲照东), Ling-hui Xia  (夏凌辉) & Mei Hong  (洪 梅)

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  1. Di-min Nie  (聂第敏)
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  2. Qiu-ling Wu  (吴秋玲)
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  4. Ran Zhang  (张 然)
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Correspondence to Mei Hong  (洪 梅).

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These authors contributed equally to this work.

This study was supported by grants from the National Natural Science Foundation of China (No. 81172826) and Collaborative Innovation Center of Hematology, China.

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Nie, Dm., Wu, Ql., Zhu, Xx. et al. Angiogenic factors are associated with development of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 35, 694–699 (2015). https://doi.org/10.1007/s11596-015-1492-4

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  • DOI: https://doi.org/10.1007/s11596-015-1492-4

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