Regulation of vascular endothelial growth factor bioactivity in patients with acute lung injury. Issue 2 (28th January 2005)

• Record Type: Journal Article
• Authors: Perkins, G D; Roberts, J; McAuley, D F; Armstrong, L; Millar, A; Gao, F; Thickett, D R
• Is Part Of: Thorax. Volume 60:Issue 2(2005)
• Page Start: 153
• Page End: 158
• Publication Date: 2005-01-28
• Subjects: 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; acute lung injury -- vascular endothelial growth factor -- acute respiratory distress syndrome; Chest -- Diseases -- Periodicals; Thorax; Chest -- Diseases; Periodicals; Periodicals; 617.54
• DOI: 10.1136/thx.2004.027912
• Languages: English
• ISSNs: 0040-6376

Abstract

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 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.