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VEGF synthesis and VEGF receptor 2 expression in patients with bronchiolitis obliterans syndrome after lung transplantation

Larsson-Callerfelt, Anna-Karin LU orcid ; Müller, Catharina LU ; Andersson-Sjöland, Annika LU ; Thiman, Lena LU ; Larsson, Hillevi LU ; Hallgren, Oskar LU ; Bjermer, Leif LU ; Eriksson, Leif LU and Westergren-Thorsson, Gunilla LU (2020) In Respiratory Medicine 166.
Abstract

OBJECTIVES: 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.

METHODS: 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... (More)

OBJECTIVES: 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.

METHODS: 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).

RESULTS: 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).

CONCLUSIONS: Our results support that changes in VEGF/VEGFR2 axis could be involved in BOS development and marker of poor outcome.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Respiratory Medicine
volume
166
article number
105944
publisher
Elsevier
external identifiers
  • pmid:32250877
  • scopus:85082427608
ISSN
1532-3064
DOI
10.1016/j.rmed.2020.105944
language
English
LU publication?
yes
additional info
Copyright © 2020 Elsevier Ltd. All rights reserved.
id
08585de9-a385-421f-96da-fb7447a9013f
date added to LUP
2020-05-27 15:15:08
date last changed
2024-03-04 20:15:45
@article{08585de9-a385-421f-96da-fb7447a9013f,
  abstract     = {{<p>OBJECTIVES: 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.</p><p>METHODS: 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).</p><p>RESULTS: 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 &lt; 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 &lt; 0.001).</p><p>CONCLUSIONS: Our results support that changes in VEGF/VEGFR2 axis could be involved in BOS development and marker of poor outcome.</p>}},
  author       = {{Larsson-Callerfelt, Anna-Karin and Müller, Catharina and Andersson-Sjöland, Annika and Thiman, Lena and Larsson, Hillevi and Hallgren, Oskar and Bjermer, Leif and Eriksson, Leif and Westergren-Thorsson, Gunilla}},
  issn         = {{1532-3064}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Respiratory Medicine}},
  title        = {{VEGF synthesis and VEGF receptor 2 expression in patients with bronchiolitis obliterans syndrome after lung transplantation}},
  url          = {{http://dx.doi.org/10.1016/j.rmed.2020.105944}},
  doi          = {{10.1016/j.rmed.2020.105944}},
  volume       = {{166}},
  year         = {{2020}},
}