Abnormal pattern of Tie-2 and vascular endothelial growth factor receptor expression in human cerebral arteriovenous malformations
Document Type
Article
Abstract
OBJECTIVE: Human cerebral arteriovenous malformations (AVMs) are speculated to result from abnormal angiogenesis. Vascular endothelial growth factor receptors (VEGF-Rs) and Tie-2 play critical roles in vasculogenesis and angiogenesis. We hypothesized that the abnormal vascular phenotype of AVMs may be associated with abnormal expression of VEGF-Rs and Tie-2. METHODS: We measured the expression of Tie-2, VEGF-R1, and VEGF-R2 in AVMs and normal brain tissue, using immunoblotting. To assess active vascular remodeling, we also measured endothelial nitric oxide synthase expression. CD31 expression was used to control for endothelial cell mass for Tie-2, VEGF-Rs, and endothelial nitric oxide synthase. Immunoblotting data were presented as relative expression, using normal brain tissue values as 100%. RESULTS: CD31 was expressed to similar degrees in AVMs and normal brain tissue (99 ± 29% versus 100 ± 20%, mean ± standard error, P = 0.98). Tie-2 expression was markedly decreased in all AVMs, compared with normal brain tissue (16 ± 9% versus 100 ± 37%, P = 0.04). VEGF-R1 expression was decreased in four of five AVMs, but the difference between the mean values was not significant (35 ± 8% versus 100 ± 42%, P = 0.14). VEGF-R2 expression was decreased in all AVMs, compared with normal brain tissue (28 ± 6% versus 100 ± 29%, P = 0.03). There was no difference in endothelial nitric oxide synthase expression between AVMs and normal brain tissue (106 ± 42% versus 100 ± 25%, P = 0.91). CONCLUSION: AVM vessels exhibited abnormal expression of Tie-2 and VEGF-Rs, both of which may contribute to the pathogenesis of AVMs.
Keywords
Cerebral arteriovenous malformations, Endothelium, Nitric oxide synthase, Receptor protein tyrosine kinase
Publication Date
1-1-2000
Publication Title
Neurosurgery
ISSN
0148396X
Volume
47
Issue
4
First Page
910
Last Page
919
PubMed ID
11014431
Digital Object Identifier (DOI)
10.1097/00006123-200010000-00022
Recommended Citation
Hashimoto, Tomoki; Emala, Charles W.; Joshi, Shailendra; Mesa-Tejada, Ricardo; Quick, Christopher M.; Feng, Lei; Libow, Adam; Marchuk, Douglas A.; and Young, William L., "Abnormal pattern of Tie-2 and vascular endothelial growth factor receptor expression in human cerebral arteriovenous malformations" (2000). Translational Neuroscience. 1656.
https://scholar.barrowneuro.org/neurobiology/1656