Regulation of vascular endothelial growth factor bioactivity in patients with acute lung injury
- 1Intensive Care Unit, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham, UK
- 2Lung Research Group, University of Bristol Medical School Unit, Southmead Hospital, Bristol, UK
- 3Lung Injury Fibrosis Treatment Programme, University of Birmingham, Lung Investigation Unit, Nuffield House, Queen Elizabeth Hospital, Birmingham, UK
- Correspondence to:
Dr D Thickett
Lung Injury Fibrosis Treatment Programme, University of Birmingham, Lung Investigation Unit, Nuffield House, Queen Elizabeth Hospital, Birmingham B15 2TT, UK;
- Received 7 May 2004
- Accepted 23 November 2004
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 α.
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.
- ALI, acute lung injury
- ARDS, acute respiratory distress syndrome
- ELF, epithelial lining fluid
- LIS, lung injury score
- TNFα, tumour necrosis factor α
- VEGF, vascular endothelial growth factor
JR was funded by UHB charities. GP was funded by West Medicals Intensive Care Society.
Gene sequencing was supported by BBSRC grant 6/JIF13209.
Conflicts of interest: none declared.