Perkins, Gavin D., Roberts, Jonathan, McAuley, Daniel F., Armstrong, L., Millar, Ann, Smith, F. Gao and Thickett, David R. (2005) Regulation of vascular endothelial growth factor bioactivity in patients with acute lung injury. Thorax, Vol.60 (No.2). pp. 153-158. doi:10.1136/thx.2004.027912

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Abstract

Background: Reduced bioactive vascular endothelial growth factor (VEGF) has been demonstrated in
several inflammatory lung conditions including the acute respiratory distress syndrome (ARDS). sVEGFR-1,
a soluble form of VEGF-1 receptor, is a potent natural inhibitor of VEGF. We hypothesised that sVEGFR-1
plays an important role in the regulation of the bioactivity of VEGF within the lung in patients with ARDS.
Methods: Forty one patients with ARDS, 12 at risk of developing ARDS, and 16 normal controls were
studied. Bioactive VEGF, total VEGF, and sVEGFR-1 were measured by ELISA in plasma and
bronchoalveolar lavage (BAL) fluid. Reverse transcriptase polymerase chain reaction for sVEGFR-1 was
performed on BAL cells.
Results: sVEGFR-1 was detectable in the BAL fluid of 48% (20/41) of patients with early ARDS (1.4–
54.8 ng/ml epithelial lining fluid (ELF)) compared with 8% (1/12) at risk patients (p = 0.017) and none of
the normal controls (p = 0.002). By day 4 sVEGFR-1 was detectable in only 2/18 ARDS patients
(p = 0.008). Patients with detectable sVEGFR-1 had lower ELF median (IQR) levels of bioactive VEGF than
those without detectable sVEGFR-1 (1415.2 (474.9–3192) pg/ml v 4761 (1349–7596.6) pg/ml, median
difference 3346 pg/ml (95% CI 305.1 to 14711.9), p = 0.016), but there was no difference in total VEGF
levels. BAL cells expressed mRNA for sVEGFR-1 and produced sVEGFR-1 protein which increased
following incubation with tumour necrosis factor a.
Conclusion: This study shows for the first time the presence of sVEGFR-1 in the BAL fluid of patients with
ARDS. This may explain the presence of reduced bioactive VEGF in patients early in the course of ARDS.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Respiratory distress syndrome, Adult, Vascular endothelial growth factors, Lungs -- Physiology
Journal or Publication Title:	Thorax
Publisher:	BMJ Group
ISSN:	0040-6376
Official Date:	2005
Dates:	Date Event 2005 Published
Volume:	Vol.60
Number:	No.2
Page Range:	pp. 153-158
DOI:	10.1136/thx.2004.027912
Status:	Peer Reviewed
Access rights to Published version:	Restricted or Subscription Access
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), University Hospitals Birmingham NHS Foundation Trust, West Midlands Intensive Care Society
Grant number:	6/JIF13209 (BBSRC)

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