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.


CONCLUSIONS
Endothelial cells derived from cerebral AVMs are highly activated cells overexpressing proangiogenic growth factors and exhibiting abnormal functions consistent with highly activated endothelial cells.
Jabbour
Mark N
MN
Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Elder
James B
JB
Samuelson
Christian G
CG
Khashabi
Shabnam
S
Hofman
Florence M
FM
Giannotta
Steven L
SL
Liu
Charles Y
CY
D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000098:blood supply / Q000166:cytology* / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D019332:Endothelin-1 / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000096:biosynthesis; D002538:Intracranial Arteriovenous Malformations / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D014841:von Willebrand Factor / Q000096:biosynthesis
D019332:Endothelin-1; D016209:Interleukin-8; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor