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Updated: Jul 18, 2026
Kinetic Analysis of Vasculogenesis Quantifies Dynamics of Vasculogenesis and Angiogenesis In Vitro
Published on: January 31, 2018
Serum vascular endothelial growth factor in cyanotic congenital heart disease functionally contributes to endothelial
Hiromichi Hamada1, Ryota Ebata, Kouji Higashi
1Department of Pediatrics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan.
Insights
Vascular endothelial growth factor (VEGF) in patient serum promotes blood vessel growth in children with cyanotic congenital heart disease. This effect on angiogenesis normalized after heart repair, highlighting VEGF's role.
Area of Science:
- Cardiovascular Research
- Angiogenesis Studies
- Pediatric Cardiology
Background:
- Cyanotic congenital heart disease (CCHD) is associated with significant neovascularization.
- The specific factors driving angiogenesis in CCHD remain unclear.
Purpose of the Study:
- To investigate the functional angiogenic molecules present in the serum of patients with CCHD.
- To understand the role of these molecules in endothelial cell behavior.
Main Methods:
- Serum angiogenic activity was assessed using human umbilical vein endothelial cells (HUVECs) in 21 CCHD patients and 17 controls.
- In vitro angiogenesis assays were performed using inhibitors and neutralizing antibodies against angiogenic molecules.
- Vascular endothelial growth factor (VEGF) was specifically investigated.
Main Results:
- Patient serum demonstrated significantly higher angiogenic activity, promoting HUVEC tube formation and migration compared to controls.
- This enhanced angiogenic activity in serum normalized post-cardiac repair.
- Inhibition of vascular endothelial growth factor receptor (VEGFR) signaling reduced serum angiogenic activity, which was reversed by recombinant VEGF.
Conclusions:
- Serum vascular endothelial growth factor (VEGF) plays a functional role in endothelial cell kinetics in patients with CCHD.
- VEGF is a key contributor to the neovascularization observed in CCHD.
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.
Methods And 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.
Conclusion:
Our results indicate that serum VEGF functionally contributes to vascular endothelial cell kinetics in patients with cyanotic congenital heart disease.
