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Pediatric reference values of VEGF-D derived from a German population-based cohort of healthy children
Maria Arélin1, Frauke Hornemann2, Andreas Merkenschlager1
1Hospital for Children and Adolescents and Center for Pediatric Research (CPL), University of Leipzig 04103 Leipzig, Germany.
Insights
Pediatric Vascular Endothelial Growth Factor D (VEGF-D) serum levels vary by age and gender, with girls showing higher levels post-puberty. These findings are crucial for early lymphangioleiomyomatosis (LAM) detection in young women with tuberous sclerosis complex (TSC).
Area of Science:
- Biomarker discovery and validation
- Pediatric endocrinology and metabolism
- Vascular and lymphatic biology
Background:
- Vascular endothelial growth factor D (VEGF-D) is implicated in blood and lymphatic vessel development and elevated in certain tumors.
- VEGF-D is a biomarker for lymphangioleiomyomatosis (LAM) in adult tuberous sclerosis complex (TSC) patients, but pediatric reference values are unknown.
- Establishing pediatric VEGF-D reference ranges is essential for early disease detection in at-risk children.
Purpose of the Study:
- To establish reliable pediatric reference values for serum VEGF-D levels in healthy children and adolescents.
- To investigate age- and gender-specific variations in pediatric VEGF-D serum concentrations.
Main Methods:
- Analysis of 2003 serum samples from healthy children aged 0.25-18 years from the prospective 'LIFE Child' cohort study.
- Quantification of serum VEGF-D levels using enzyme-linked immunoassay (ELISA).
Main Results:
- Serum VEGF-D levels exhibit significant age- and gender-specific variations in healthy children and adolescents.
- A notable difference in post-pubertal VEGF-D levels was observed between girls and boys.
- Elevated post-pubertal VEGF-D levels in girls suggest a role for estrogen metabolism in VEGF-D-mediated processes.
Conclusions:
- Pediatric VEGF-D reference values are crucial for identifying early disease progression, particularly LAM in young women with TSC.
- Further research is warranted to explore the impact of estrogen metabolism on VEGF-D levels in pediatric populations.
- These findings provide a foundation for utilizing VEGF-D as a diagnostic tool in pediatric TSC and LAM management.
Background:
Vascular endothelial growth factor D (VEGF-D) is a growth-factor involved in the development of blood vessels and lymphatics in tissues all over the human body. Interestingly, VEGF-D serum levels are increased in certain tumor entities. For tuberous sclerosis complex (TSC), a rare genetic disease associated with (benign) tumor growth, VEGF-D is already implemented as a diagnostic and therapeutic biomarker to monitor onset and progress of lymphangioleiomyomatosis (LAM), one of the noncancerous tumor manifestations in mainly female adult TSC patients. To date only adult VEGF-D serum cut off values are established and used as a diagnostic tool in LAM. Neither cut off nor pediatric reference values for VEGF-D serum levels are known, our study aims to provide reliable pediatric VEGF-D results in samples from healthy children and adolescents.
Methods:
We analyzed 2003 samples provided by healthy children aged 0.25-18 years participating in the prospective longitudinal population-based cohort study "LIFE Child" in Leipzig, Germany. Serum VEGF-D levels were measured by enzyme-linked immunoassay.
Results:
VEGF-D levels in healthy children and adolescents show age-and gender specific variations. We showed a significant difference between girls and boys in post pubertal VEGF-D levels. Especially the fact, that girls showed higher VEGF-D levels with advancing stages of puberty is underlining the importance of estrogen metabolism in context of VEGF-D mediated cell proliferation, angiogenesis and associated disease mechanisms.
Conclusion:
Knowing VEGF-D levels in growing healthy young children and adolescents could help to recognize early disease progression of LAM in individuals at risk especially young women suffering from TSC. Further studies are needed on VEGF-D serum levels in children, especially the impact of estrogen metabolism on VEGF-D should be investigated further.

