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).


CONCLUSIONS
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.
Medford
Andrew R L
ARL
Lung Research Group, Division of Medicine, University of Bristol, Southmead Hospital, Westbury-on-Trym, Bristol, UK.
Godinho
Sofia I H
SIH
Lung Research Group, Division of Medicine, University of Bristol, Southmead Hospital, Westbury-on-Trym, Bristol, UK.
Keen
Leigh J
LJ
Department of Pathology and Microbiology, Homeopathic Hospital Site, University of Bristol, Bristol, UK.
Bidwell
Jeffrey L
JL
Department of Pathology and Microbiology, Homeopathic Hospital Site, University of Bristol, Bristol, UK.
Millar
Ann B
AB
Lung Research Group, Division of Medicine, University of Bristol, Southmead Hospital, Westbury-on-Trym, Bristol, UK. Electronic address: Ann.Millar@bristol.ac.uk.
D000368:Aged; D000483:Alleles; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004198:Disease Susceptibility / Q000453:epidemiology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011336:Probability; D011379:Prognosis; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D018570:Risk Assessment; D012494:Sampling Studies; D012720:Severity of Illness Index; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors