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...
Main Authors: | , , , , , , |
---|---|
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 |
_version_ | 1830296824613699584 |
---|---|
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. |
first_indexed | 2024-12-19T07:22:08Z |
format | Article |
id | doaj.art-e69dd85f797048cab52d239a1fc55d77 |
institution | Directory Open Access Journal |
issn | 1749-8090 |
language | English |
last_indexed | 2024-12-19T07:22:08Z |
publishDate | 2019-01-01 |
publisher | BMC |
record_format | Article |
series | Journal of Cardiothoracic Surgery |
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 |
work_keys_str_mv | AT haichaoxu theroleofhif1avegfpathwayinbronchiolitisobliteransafterlungtransplantation AT abudumailamuabuduwufuer theroleofhif1avegfpathwayinbronchiolitisobliteransafterlungtransplantation AT wanglv theroleofhif1avegfpathwayinbronchiolitisobliteransafterlungtransplantation AT zhenyuzhou theroleofhif1avegfpathwayinbronchiolitisobliteransafterlungtransplantation AT yunhaiyang theroleofhif1avegfpathwayinbronchiolitisobliteransafterlungtransplantation AT chongzhang theroleofhif1avegfpathwayinbronchiolitisobliteransafterlungtransplantation AT jianhu theroleofhif1avegfpathwayinbronchiolitisobliteransafterlungtransplantation AT haichaoxu roleofhif1avegfpathwayinbronchiolitisobliteransafterlungtransplantation AT abudumailamuabuduwufuer roleofhif1avegfpathwayinbronchiolitisobliteransafterlungtransplantation AT wanglv roleofhif1avegfpathwayinbronchiolitisobliteransafterlungtransplantation AT zhenyuzhou roleofhif1avegfpathwayinbronchiolitisobliteransafterlungtransplantation AT yunhaiyang roleofhif1avegfpathwayinbronchiolitisobliteransafterlungtransplantation AT chongzhang roleofhif1avegfpathwayinbronchiolitisobliteransafterlungtransplantation AT jianhu roleofhif1avegfpathwayinbronchiolitisobliteransafterlungtransplantation |