Angiogenic proteins in the lungs of children after cavopulmonary anastomosis.
OBJECTIVE
Pulmonary arteriovenous malformations may cause progressive cyanosis after cavopulmonary anastomosis and may develop as a result of abnormal angiogenesis. We used immunohistochemistry to determine whether angiogenic proteins are increased in the lungs of children after cavopulmonary anastomosis.


METHODS
Lung specimens were obtained from 13 children after cavopulmonary anastomosis and from 6 control subjects. Specimens were stained with antibodies against vascular endothelial growth factor and its receptor (flk-1/KDR), basic fibroblast growth factor, alpha-smooth muscle actin, CD31, collagen IV, fibronectin, and proliferating cell nuclear antigen. Staining was graded on a scale of 0 to 3. Vessels positive for proliferating cell nuclear antigen were counted in 10 fields per specimen, and the results were averaged.


RESULTS
After cavopulmonary anastomosis, patients demonstrated increased staining for vascular endothelial growth factor (P =.03) and its receptor (P =.03) and decreased staining for CD31 (P =.004). Proliferating cell nuclear antigen staining in patients was equivalent to that for control subjects (P =.9).


CONCLUSIONS
Lung biopsy specimens from children after cavopulmonary anastomosis demonstrate increased expression of vascular endothelial growth factor and its receptor. These data confirm earlier findings that blood vessels forming after cavopulmonary anastomosis may have reduced intercellular junctions (decreased CD31 staining). Despite the increased numbers of pulmonary vessels that are present in these patients, these vessels are not highly proliferative (proliferating cell nuclear antigen staining equivalent to that of control subjects). These results suggest that vascular endothelial growth factor may be a mediator of angiogenesis in the lungs of children after cavopulmonary anastomosis; however, other factors, such as vascular dilation and remodeling, may also be important.
Starnes
S L
SL
Division of Cardiac Surgery, Children's Hospital and Regional Medical Center, Seattle, Wash, USA.
Duncan
B W
BW
Kneebone
J M
JM
Rosenthal
G L
GL
Patterson
K
K
Fraga
C H
CH
Kilian
K M
KM
Mathur
S K
SK
Lupinetti
F M
FM
D000293:Adolescent; D001165:Arteriovenous Malformations / Q000209:etiology* / Q000473:pathology* / Q000601:surgery; D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003490:Cyanosis / Q000209:etiology* / Q000473:pathology*; D018450:Disease Progression; D016228:Endothelial Growth Factors / Q000032:analysis*; D018729:Fontan Procedure; D018610:Heart Bypass, Right / Q000009:adverse effects*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008222:Lymphokines / Q000032:analysis*; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000473:pathology* / Q000601:surgery; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011651:Pulmonary Artery / Q000002:abnormalities*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D017978:Receptors, Growth Factor / Q000032:analysis*; D040262:Receptors, Vascular Endothelial Growth Factor; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018809:Proliferating Cell Nuclear Antigen; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor