Serum vascular endothelial growth factor in cyanotic congenital heart disease functionally contributes to endothelial cell kinetics in vitro.
BACKGROUND
Remarkable amounts of neovascularization develop in patients with cyanotic congenital heart disease who have low pulmonary blood flow and systemic cyanosis, but the factors functionally responsible for angiogenesis in cyanotic congenital heart disease have not been determined.


RESULTS
To investigate the functional angiogenic molecules in serum from these patients, serum angiogenic activity was studied in 21 patients (systemic oxygen saturation: 82+/-1.9%) and in 17 healthy controls. Patient serum was more active in stimulating the tube formation of human umbilical vein endothelial cells (HUVECs) into capillary-like structures than control serum (150% vs 104% of internal control; p<0.001). This increased serum angiogenic activity normalized after total cardiac repair (p<0.001). The migration activity of HUVECs was also accelerated in patient serum (p=0.007). To identify the molecules in patient serum affecting tube formation of HUVECs, we examined the effects of an inhibitor or a neutralizing antibody against various angiogenic molecules on in vitro angiogenesis. Both the soluble vascular endothelial growth factor (VEGF) receptor 1 and the VEGF receptor 2 tyrosine kinase inhibitor SU5416 reduced the basal serum angiogenic activity of patients and this was reversed by a supplement of recombinant human VEGF.


CONCLUSIONS
Our results indicate that serum VEGF functionally contributes to vascular endothelial cell kinetics in patients with cyanotic congenital heart disease.
Hamada
Hiromichi
H
Department of Pediatrics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan.
Ebata
Ryota
R
Higashi
Kouji
K
Tateno
Shigeru
S
Niwa
Koichiro
K
Honda
Takafumi
T
Yasukawa
Kumi
K
Terai
Masaru
M
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D002465:Cell Movement; D002648:Child; D002675:Child, Preschool; D003490:Cyanosis / Q000503:physiopathology*; D042783:Endothelial Cells / Q000502:physiology*; D006330:Heart Defects, Congenital / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D018919:Neovascularization, Physiologic / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
D042461:Vascular Endothelial Growth Factor A