Decreased VEGF concentration in lung tissue and vascular injury during ARDS.
Endothelial injury is an important prognostic factor in acute respiratory distress syndrome (ARDS). Decreased production of vascular endothelial growth factor (VEGF) in ARDS may favour vascular lesions, since VEGF promotes endothelial survival by inhibiting apoptosis. This study sought to document low VEGF levels in lung tissue from ARDS patients, to determine whether the cause was injury to alveolar type II cells (the main pulmonary source of VEGF) and to evaluate the vascular consequences. Lung specimens were obtained by open biopsy or autopsy from 29 patients with severe ARDS (two survivors) and five controls. As compared with controls, homogenates of lung tissue from ARDS patients contained less VEGF (median (interquartile range) ARDS 8.2 (4.7-12.2) versus controls 28.4 (9.9-47.1) ng x g(-1) protein). Increased immunostaining with surfactant protein B was seen in ARDS lungs. Extensive cellular apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling staining), including endothelial and alveolar type II cells, was demonstrated, and vascular bed density (CD31 immunostaining) decreased in ARDS lungs as compared with controls. VEGF levels were negatively correlated to apoptotic endothelial cell counts. In conclusion, decreased vascular endothelial growth factor levels in lung tissue may participate in the decrease in lung perfusion in acute respiratory distress syndrome.
Abadie
Y
Y
INSERM Unit 492, Paris XII Unversity, France.
Bregeon
F
F
Papazian
L
L
Lange
F
F
Chailley-Heu
B
B
Thomas
P
P
Duvaldestin
P
P
Adnot
S
S
Maitre
B
B
Delclaux
C
C
D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D016022:Case-Control Studies; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012016:Reference Values; D012128:Respiratory Distress Syndrome / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D015996:Survival Rate; D014652:Vascular Diseases / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000378:metabolism*
D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A