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Updated: Feb 8, 2026
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Elevated serum vascular endothelial growth factor and development of cardiac allograft vasculopathy in children
Kae Watanabe1, Anis Karimpour-Fard2, Alix Michael1
1Division of Cardiology, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA.
Insights
Serum vascular endothelial growth factor-A (VEGF) is elevated in pediatric heart transplant recipients before cardiac allograft vasculopathy (CAV) diagnosis. This finding suggests VEGF is a useful predictive biomarker for CAV development.
Area of Science:
- Cardiology
- Immunology
- Biomarker Research
Background:
- Cardiac allograft vasculopathy (CAV) is a primary cause of retransplantation and mortality in pediatric heart transplant recipients.
- Understanding biomarkers for early CAV detection is critical for improving patient outcomes.
Purpose of the Study:
- To investigate the association between serum vascular endothelial growth factor-A (VEGF) levels and the development of CAV in pediatric heart transplant recipients.
Main Methods:
- Retrospective analysis of banked serum samples from pediatric heart transplant recipients undergoing cardiac catheterization.
- VEGF concentrations measured using enzyme-linked immunosorbent assay (ELISA).
- Serum samples collected at multiple time-points relative to CAV diagnosis (pre-CAV and CAV) or a single time-point for controls (no-CAV).
Main Results:
- Serum VEGF levels were significantly elevated in pediatric heart transplant recipients prior to catheter-based diagnosis of CAV (pre-CAV mean: 316.2 ± 118.3 pg/ml vs. no-CAV mean: 144.0 ± 89.05 pg/ml; p = 0.0002).
- Receiver-operating characteristic (ROC) curve analysis indicated that pre-CAV VEGF levels could predict CAV development with 77.8% sensitivity and 91.7% specificity at a threshold of 226.3 pg/ml (Area Under Curve = 87.7%, p = 0.0002).
- Elevated VEGF levels were observed in patients with both angiographically confirmed CAV and those with intravascular ultrasound (IVUS)-detected CAV.
Conclusions:
- Elevated serum VEGF preceding detectable CAV highlights its potential as a predictive biomarker.
- Further research into the role of VEGF in the pathogenesis of CAV within the pediatric heart transplant population is warranted.
Background:
Cardiac allograft vasculopathy (CAV) is a leading cause of retransplantation and death in pediatric heart transplant recipients. Our aim was to evaluate the association between serum vascular endothelial growth factor-A (VEGF) and CAV development in the pediatric heart transplant population.
Methods:
In this retrospective study performed at a university hospital, VEGF concentrations were measured by enzyme-linked immunosorbent assay in banked serum from pediatric heart transplant recipients undergoing routine cardiac catheterization. In subjects with CAV (n = 29), samples were obtained at 2 time-points: before CAV diagnosis (pre-CAV) and at the time of initial CAV diagnosis (CAV). In subjects without CAV (no-CAV, n = 16), only 1 time-point was used. VEGF concentrations (n = 74) were assayed in duplicate.
Results:
Serum VEGF is elevated in pediatric heart transplant recipients before catheter-based diagnosis of CAV (no-CAV mean: 144.0 ± 89.05 pg/ml; pre-CAV mean: 316.2 ± 118.3 pg/ml; p = 0.0002). Receiver-operating characteristic curve analysis of pre-CAV VEGF levels demonstrated an area under the curve of 87.7% (p = 0.0002), with a VEGF level of 226.3 pg/ml predicting CAV development with 77.8% sensitivity and 91.7% specificity. VEGF is similarly elevated in subjects with angiographically diagnosed CAV and in those with normal angiography but intravascular ultrasound (IVUS) evidence of CAV.
Conclusions:
The increase in serum VEGF before onset of detectable CAV is fundamental to its utility as a predictive biomarker and suggests further investigations of VEGF in the pathogenesis of CAV are warranted in the pediatric heart transplant population.
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