Aberrant Angiogenic Characteristics of Human Brain Arteriovenous Malformation Endothelial Cells

Objective: To identify and characterize the phenotypic and functional differences of endothelial cells derived from cerebral arteriovenous malformations (AVM), as compared with endothelial cells derived from a normal brain. Methods: Isolated AVM brain endothelial cells and control brain endothelial cells were evaluated immunohistochemically for expression of the endothelial cell markers von Willebrand factor and CD31, as well as angiogenic factors including vascular endothelial growth factor A, interleukin-8, and endothelin-1. Vascular endothelial growth factor receptors 1 and 2 were also evaluated using immunohistochemistry techniques. Functional assays evaluated cell proliferation, cytokine production, tubule formation, and cell migration using the modified Boyden chamber technique. Results: Endothelial cells derived from AVMs expressed high levels of vascular endothelial growth factor A and significantly overexpressed the vascular endothelial growth factor receptors 1 and 2 (P < 0.05), as compared with control endothelial cells. In addition, comparison to control brain endothelial cells demonstrated that AVM brain endothelial cells proliferated faster, migrated more quickly, and produced aberrant tubule-like structures. Conclusion: Endothelial cells derived from cerebral AVMs are highly activated cells overexpressing proangiogenic growth factors and exhibiting abnormal functions consistent with highly activated endothelial cells