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Updated: Aug 4, 2026
Angiogenesis in the Ischemic Rat Lung
Published on: February 8, 2013
Angiogenic proteins in the lungs of children after cavopulmonary anastomosis
S L Starnes1, B W Duncan, J M Kneebone
1Division of Cardiac Surgery, Children's Hospital and Regional Medical Center, Seattle, Wash, USA.
Insights
Children undergoing cavopulmonary anastomosis show increased vascular endothelial growth factor (VEGF) and its receptor in lung tissue. This suggests VEGF may drive abnormal blood vessel formation after this heart surgery.
Area of Science:
- Cardiovascular Surgery
- Pulmonary Hypertension
- Pediatric Cardiology
Background:
- Pulmonary arteriovenous malformations (PAVMs) can cause cyanosis post-cavopulmonary anastomosis.
- Abnormal angiogenesis is implicated in PAVM development.
- Understanding angiogenic factors is crucial for managing post-surgical complications.
Purpose of the Study:
- To investigate the expression of angiogenic proteins in pediatric patients following cavopulmonary anastomosis.
- To determine if vascular endothelial growth factor (VEGF) and its receptor are elevated in lung tissue after this procedure.
Main Methods:
- Immunohistochemistry was used on lung specimens from 13 post-cavopulmonary anastomosis patients and 6 controls.
- Antibodies targeted VEGF, its receptor (flk-1/KDR), and other markers like CD31 and proliferating cell nuclear antigen.
- Staining intensity was graded, and cell proliferation was quantified.
Main Results:
- Increased staining for VEGF and its receptor was observed in patients (P=.03).
- Decreased CD31 staining, indicating reduced intercellular junctions, was noted (P=.004).
- Proliferating cell nuclear antigen staining was similar between patients and controls (P=.9).
Conclusions:
- Lung tissue after cavopulmonary anastomosis shows elevated VEGF and its receptor.
- These findings support VEGF's role in angiogenesis post-surgery.
- Reduced intercellular junctions and non-proliferative vessels suggest complex vascular remodeling processes.
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.
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