The role of HIF-1α-VEGF pathway in bronchiolitis obliterans after lung transplantation.
Animals
Bronchiolitis Obliterans
/ blood
Disease Models, Animal
Humans
Hypoxia
/ complications
Hypoxia-Inducible Factor 1, alpha Subunit
/ blood
Immunohistochemistry
Lung Transplantation
Male
Postoperative Complications
/ blood
Rats
Vascular Endothelial Growth Factor A
/ blood
Vascular Endothelial Growth Factor Receptor-2
/ blood
Bronchiolitis obliterans
Fibrosis
Hypoxia-inducible factor 1, alpha subunit
Lung transplantation
Vascular endothelial growth factor a
Journal
Journal of cardiothoracic surgery
ISSN: 1749-8090
Titre abrégé: J Cardiothorac Surg
Pays: England
ID NLM: 101265113
Informations de publication
Date de publication:
29 Jan 2019
29 Jan 2019
Historique:
received:
26
06
2018
accepted:
08
01
2019
entrez:
31
1
2019
pubmed:
31
1
2019
medline:
8
3
2019
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 30696477
doi: 10.1186/s13019-019-0832-z
pii: 10.1186/s13019-019-0832-z
pmc: PMC6352448
doi:
Substances chimiques
Hypoxia-Inducible Factor 1, alpha Subunit
0
Vascular Endothelial Growth Factor A
0
Vascular Endothelial Growth Factor Receptor-2
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
27Subventions
Organisme : National Natural Science Foundation of China
ID : 81373161
Organisme : The Health Department of Zhejiang province
ID : 2012ZDA014
Organisme : The Health Department of Zhejiang province
ID : 2012ZDA017
Organisme : The Health Department of Zhejiang province
ID : 2012KYA081
Organisme : Chinese Medicine Research Program of Zhejiang Province
ID : 2012ZQ016
Références
Am J Respir Cell Mol Biol. 1999 May;20(5):924-34
pubmed: 10226062
Circ Res. 2000 Oct 13;87(8):644-7
pubmed: 11029398
J Heart Lung Transplant. 2002 Mar;21(3):297-310
pubmed: 11897517
Curr Opin Crit Care. 2002 Jun;8(3):242-50
pubmed: 12386504
Blood. 2003 Mar 15;101(6):2253-60
pubmed: 12411310
Ann Thorac Surg. 2004 May;77(5):1751-5
pubmed: 15111179
Folia Microbiol (Praha). 2004;49(5):499-505
pubmed: 15702536
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):5109-14
pubmed: 17360382
Eur J Cardiothorac Surg. 2007 Jul;32(1):35-41
pubmed: 17481912
J Heart Lung Transplant. 2007 Dec;26(12):1229-42
pubmed: 18096473
J Clin Invest. 2011 Jun;121(6):2336-49
pubmed: 21606594
J Clin Invest. 2011 Jun;121(6):2155-7
pubmed: 21606603
Cell Immunol. 2012;273(1):59-66
pubmed: 22192476
PLoS One. 2012;7(1):e29802
pubmed: 22238655
Cell. 2012 Feb 3;148(3):399-408
pubmed: 22304911
J Heart Lung Transplant. 2012 Feb;31(2):213-21
pubmed: 22305384
Exp Lung Res. 2012 Apr;38(3):111-23
pubmed: 22394285
PLoS One. 2012;7(6):e39265
pubmed: 22745725
J Heart Lung Transplant. 2013 Nov;32(11):1131-9
pubmed: 24050896
Am J Transplant. 2014 Jul;14(7):1481-7
pubmed: 24909061
Mol Cells. 2014 Jun;37(6):487-96
pubmed: 24938229
Exp Cell Res. 2015 Jan 15;330(2):371-81
pubmed: 25107382
Curr Opin Organ Transplant. 2014 Oct;19(5):460-7
pubmed: 25144668
Am J Transplant. 2015 Jul;15(7):1793-1804
pubmed: 25773063
J Investig Med. 2016 Feb;64(2):361-3
pubmed: 25955799
J Heart Lung Transplant. 2015 Oct;34(10):1264-77
pubmed: 26454740
Clin Transplant. 2017 May;31(5):
pubmed: 28244139
Clin Transplant. 2018 Jan;32(1):
pubmed: 29151274