Relationship between vascular endothelial growth factor + 936 genotype and plasma/epithelial lining fluid vascular endothelial growth factor protein levels in patients with and at risk for ARDS

BACKGROUND: Vascular endothelial growth factor (VEGF) is postulated to have a role in ARDS. The functional VEGF + 936 polymorphic T allele is associated with an increased susceptibility to and severity of ARDS. The reasons for this are unclear. We hypothesized that the T allele would be associated with an alteration in the relation between epithelial lining fluid (ELF) and plasma VEGF levels as a potential explanation for its association with susceptibility to and severity of ARDS. METHODS: Plasma and ELF VEGF protein levels were measured by enzyme-linked immunosorbent assay from 10 at-risk patients receiving mechanical ventilation and 16 ARDS patients with the T allele, as well as 18 at-risk patients receiving mechanical ventilation and 26 ARDS patients without the T allele (wild-type CC genotype). RESULTS: The T allele was associated with a significantly lower mean ELF VEGF level in ARDS patients (2,090 +/- 758 pg/mL vs 3,292 +/- 865 pg/mL, p <0.05) and mean ELF/plasma VEGF level ratio (13.7 +/- 4.6 pg/mL vs 94.7 +/- 51.2 pg/mL, p <0.01). There was no relation between the T allele and plasma VEGF level, oxygenation, or acute physiology score in at-risk and ARDS patients. ELF VEGF levels were significantly higher than plasma levels in both cohorts except for at-risk patients without the T allele (wild-type CC genotype). CONCLUSION: The T allele is associated with a significant decrease in ELF levels and the ELF/plasma ratio in ARDS patients. This may explain the increased susceptibility and physiologic derangement in ARDS patients with the T allele. We speculate VEGF has a protective function in the lung. Further studies are necessary to clarify the underlying mechanisms.