VEGF synthesis and VEGF receptor 2 expression in patients with bronchiolitis obliterans syndrome after lung transplantation.
Adult
Aged
Biomarkers
/ metabolism
Bronchiolitis Obliterans
/ diagnosis
Female
Fibroblasts
/ metabolism
Gene Expression
Graft Rejection
/ diagnosis
Humans
Lung
/ cytology
Lung Transplantation
Male
Middle Aged
Prognosis
Prolyl Hydroxylases
/ genetics
Vascular Endothelial Growth Factor A
/ genetics
Vascular Endothelial Growth Factor Receptor-2
/ genetics
Young Adult
Chronic rejections
Lung transplantation
Obliterative bronchiolitis
Primary human lung fibroblasts
Vascular endothelial growth factor
Vascular endothelial growth factor receptor 2
Journal
Respiratory medicine
ISSN: 1532-3064
Titre abrégé: Respir Med
Pays: England
ID NLM: 8908438
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
31
12
2019
revised:
19
03
2020
accepted:
20
03
2020
pubmed:
7
4
2020
medline:
10
10
2020
entrez:
7
4
2020
Statut:
ppublish
Résumé
Chronic lung allograft dysfunction including Bronchiolitis obliterans syndrome (BOS) is common after lung transplantation. Histologically, BOS is recognized as fibrotic lesions with accumulated extracellular matrix (ECM) in small airways. Lung fibroblasts are major producers of ECM and vascular endothelial growth factor (VEGF). In this study we hypothesize that VEGF is involved in BOS development after lung transplantation. We investigated the effect of profibrotic transforming growth factor (TGF-β) on VEGF synthesis in lung fibroblasts isolated from distal lung tissue biopsies taken from patients at 3, 6 and 12 months after lung transplantation (n = 14). Co-expression of VEGF receptor (VEGFR) 2 and collagen marker prolyl4-hydroxylase (p4OH) were analyzed in lung tissue from patients with BOS (n = 11). VEGF synthesis from distal derived lung fibroblasts were significantly lower 3 months after lung transplantation (168.6 ± 133.7; n = 7) compared to non-transplanted subjects (451.8 ± 185.9; n = 9; p = 0.0033) and increased over time at 6 months (584.1 ± 264.9; n = 9; p = 0.0033) and 12 months (451.1 ± 207.5; n = 8; p = 0.0065) post transplantation. TGF-β significantly induced VEGF synthesis at all time points. At 12 months post transplantation there was significantly less VEGF synthesis after TGF-β stimulation in fibroblasts obtained from BOS patients (1170 ± 450.2; n = 4) compared to patients without any chronic rejection process (1980 ± 417.9; n = 4; p < 0.039). The numbers of cells expressing VEGFR2/p4OH were increased in patients with BOS (33.2 ± 10.9; n = 11) compared to control subjects (10.1 ± 9.9; n = 11; p < 0.001). Our results support that changes in VEGF/VEGFR2 axis could be involved in BOS development and marker of poor outcome.
Identifiants
pubmed: 32250877
pii: S0954-6111(20)30084-6
doi: 10.1016/j.rmed.2020.105944
pii:
doi:
Substances chimiques
Biomarkers
0
Vascular Endothelial Growth Factor A
0
Prolyl Hydroxylases
EC 1.14.11.-
KDR protein, human
EC 2.7.10.1
Vascular Endothelial Growth Factor Receptor-2
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105944Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest All authors declare no conflict of interest.