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

摘要

Background: Vascular endothelial growth factor (VEGF) is postulated to have a role in ARDS. Thenfunctional VEGF u0001 936 polymorphic T allele is associated with an increased susceptibility to andnseverity of ARDS. The reasons for this are unclear. We hypothesized that the T allele would benassociated with an alteration in the relation between epithelial lining fluid (ELF) and plasma VEGFnlevels as a potential explanation for its association with susceptibility to and severity of ARDS.nMethods: Plasma and ELF VEGF protein levels were measured by enzyme-linked immunosorbentnassay from10 at-risk patients receivingmechanical ventilation and 16 ARDS patients with the T allele,nas well as 18 at-risk patients receiving mechanical ventilation and 26 ARDS patients without the Tnallele (wild-type CC genotype).nResults: The T allele was associated with a significantly lowermean ELF VEGF level in ARDS patientsn(2,090 u0002 758 pg/mL vs 3,292 u0002 865 pg/mL, p < 0.05) and mean ELF/plasma VEGF level ration(13.7 u0002 4.6 pg/mL vs 94.7 u0002 51.2 pg/mL, p < 0.01). There was no relation between the T allele andnplasma VEGF level, oxygenation, or acute physiology score in at-risk and ARDS patients. ELF VEGFnlevels were significantly higher than plasma levels in both cohorts except for at-risk patients withoutnthe T allele (wild-type CC genotype).nConclusion: The T allele is associated with a significant decrease in ELF levels and the ELF/plasmanratio in ARDS patients. This may explain the increased susceptibility and physiologic derangement innARDS patients with the T allele. We speculate VEGF has a protective function in the lung. Furthernstudies are necessary to clarify the underlying mechanisms. (CHEST 2009; 136:457–464)