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Regulation of vascular endothelial growth factor bioactivity in patients with acute lung injury

By Gavin D. Perkins, Jonathan Roberts, Daniel F. McAuley, L. Armstrong, Ann Millar, F. Gao Smith and David R. Thickett

Abstract

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

Topics: QP
Publisher: BMJ Group
Year: 2005
OAI identifier: oai:wrap.warwick.ac.uk:34573

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