Journal of Cardiothoracic Surgery (Jan 2019)
The role of HIF-1α-VEGF pathway in bronchiolitis obliterans after lung transplantation
Abstract
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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