Regulation of vascular endothelial growth factor bioactivity in patients with acute lung injury
Perkins, Gavin D., Roberts, Jonathan (Jonathan R.), McAuley, Daniel F., Armstrong, L., Millar, Ann, 1955-, Smith, F. Gao (Fang 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. ISSN 0040-6376
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Official URL: http://dx.doi.org/10.1136/thx.2004.027912
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|
|Page Range:||pp. 153-158|
|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)|
1 Compernolle V, Brusselmans K, Acker T, et al. Loss of HIF-2alpha and
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