The role of HIF-1α-VEGF pathway in bronchiolitis obliterans after lung transplantation

Abstract Background Graft function may be affected if the organ is exposed to hypoxia. We hypothesized that bronchiolitis obliterans (BO) after lung transplantation is associated with hypoxia-inducible factor-1α (HIF-1α). This study compares the expression of HIF-1α and its downstream proteins in al...

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Main Authors: Haichao Xu, Abudumailamu Abuduwufuer, Wang Lv, Zhenyu Zhou, Yunhai Yang, Chong Zhang, Jian Hu
Format: Article
Language:English
Published: BMC 2019-01-01
Series:Journal of Cardiothoracic Surgery
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13019-019-0832-z
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author Haichao Xu
Abudumailamu Abuduwufuer
Wang Lv
Zhenyu Zhou
Yunhai Yang
Chong Zhang
Jian Hu
author_facet Haichao Xu
Abudumailamu Abuduwufuer
Wang Lv
Zhenyu Zhou
Yunhai Yang
Chong Zhang
Jian Hu
author_sort Haichao Xu
collection DOAJ
description Abstract Background Graft function may be affected if the organ is exposed to hypoxia. We hypothesized that bronchiolitis obliterans (BO) after lung transplantation is associated with hypoxia-inducible factor-1α (HIF-1α). This study compares the expression of HIF-1α and its downstream proteins in allograft and isograft to explore the relationship between this pathway and BO in rats. Material and methods We performed an orthotopic left pulmonary transplant model using the tri-cuff vascular anastomosis method and evaluated the histopathology, including the severity of fibrosis (SF). The expression of HIF-1α, VEGF-A, and VEGFR-2 was accessed by immunohistochemistry. Results The imageology and pathology showed that the allogenic model developed BO 90 days after the operation. The percentages of a high expression of HIF-1α, VEGF-A, and VEGFR-2 in the allogeneic group were 77.27, 63.64, and 68.18% higher than in the isogeneic group, respectively. The SF score was highest in the allograft and was positively correlated with the expression of the proteins. Conclusion This model can simulate human BO after lung transplantation. The expression of HIF-1α and its downstream proteins in post-transplantation was up-regulated, suggesting that activation of the HIF-1α-VEGF pathway might be involved in the occurrence and prognosis of BO.
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spelling doaj.art-e69dd85f797048cab52d239a1fc55d772022-12-21T20:30:54ZengBMCJournal of Cardiothoracic Surgery1749-80902019-01-011411810.1186/s13019-019-0832-zThe role of HIF-1α-VEGF pathway in bronchiolitis obliterans after lung transplantationHaichao Xu0Abudumailamu Abuduwufuer1Wang Lv2Zhenyu Zhou3Yunhai Yang4Chong Zhang5Jian Hu6Thoracic Surgery, The First Affiliated Hospital, Zhejiang UniversityThoracic Surgery, The First Affiliated Hospital, Zhejiang UniversityThoracic Surgery, The First Affiliated Hospital, Zhejiang UniversityThoracic Surgery, The First Affiliated Hospital, Zhejiang UniversityThoracic Surgery, The First Affiliated Hospital, Zhejiang UniversityThoracic Surgery, The First Affiliated Hospital, Zhejiang UniversityThoracic Surgery, The First Affiliated Hospital, Zhejiang UniversityAbstract Background Graft function may be affected if the organ is exposed to hypoxia. We hypothesized that bronchiolitis obliterans (BO) after lung transplantation is associated with hypoxia-inducible factor-1α (HIF-1α). This study compares the expression of HIF-1α and its downstream proteins in allograft and isograft to explore the relationship between this pathway and BO in rats. Material and methods We performed an orthotopic left pulmonary transplant model using the tri-cuff vascular anastomosis method and evaluated the histopathology, including the severity of fibrosis (SF). The expression of HIF-1α, VEGF-A, and VEGFR-2 was accessed by immunohistochemistry. Results The imageology and pathology showed that the allogenic model developed BO 90 days after the operation. The percentages of a high expression of HIF-1α, VEGF-A, and VEGFR-2 in the allogeneic group were 77.27, 63.64, and 68.18% higher than in the isogeneic group, respectively. The SF score was highest in the allograft and was positively correlated with the expression of the proteins. Conclusion This model can simulate human BO after lung transplantation. The expression of HIF-1α and its downstream proteins in post-transplantation was up-regulated, suggesting that activation of the HIF-1α-VEGF pathway might be involved in the occurrence and prognosis of BO.http://link.springer.com/article/10.1186/s13019-019-0832-zLung transplantationBronchiolitis obliteransFibrosisHypoxia-inducible factor 1, alpha subunitVascular endothelial growth factor a
spellingShingle Haichao Xu
Abudumailamu Abuduwufuer
Wang Lv
Zhenyu Zhou
Yunhai Yang
Chong Zhang
Jian Hu
The role of HIF-1α-VEGF pathway in bronchiolitis obliterans after lung transplantation
Journal of Cardiothoracic Surgery
Lung transplantation
Bronchiolitis obliterans
Fibrosis
Hypoxia-inducible factor 1, alpha subunit
Vascular endothelial growth factor a
title The role of HIF-1α-VEGF pathway in bronchiolitis obliterans after lung transplantation
title_full The role of HIF-1α-VEGF pathway in bronchiolitis obliterans after lung transplantation
title_fullStr The role of HIF-1α-VEGF pathway in bronchiolitis obliterans after lung transplantation
title_full_unstemmed The role of HIF-1α-VEGF pathway in bronchiolitis obliterans after lung transplantation
title_short The role of HIF-1α-VEGF pathway in bronchiolitis obliterans after lung transplantation
title_sort role of hif 1α vegf pathway in bronchiolitis obliterans after lung transplantation
topic Lung transplantation
Bronchiolitis obliterans
Fibrosis
Hypoxia-inducible factor 1, alpha subunit
Vascular endothelial growth factor a
url http://link.springer.com/article/10.1186/s13019-019-0832-z
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