Increased expression of ephrin A1 in brain arteriovenous malformation: DNA microarray analysis.

ABSTRACT

A number of previous studies have revealed the abnormal expression of various angiogenesis-related genes or products in brain arteriovenous malformation (AVM). To understand the molecular process of this disease, we analyzed gene expression profiles in brain AVM. Using a DNA microarray consisting of 17,086 genes, we identified differentially expressed genes in 5 brain AVMs from their draining veins, vessels retaining basic venous architecture. Not many genes were differentially expressed between the AVM nidus and the draining vein. When we applied an absolute cut-off value for normalized log2 (cy5/cy3 ratio) of 0.4, 19 genes were selected. Genes such as SOX8, TRIM2, FENA1 (ephrin A1), and AQP4 were upregulated, and genes such as I_1000105, KRT18, IGFBP7, EMILIN-2, and KRT14 were downregulated. Genes relating to angiogenesis, such as vascular endothelial growth factor and angiopoietin and other members of the ephrin family, were not differentiated. Among differentially expressed genes detected in this analysis, we focused on ephrin A1, a gene related to embryogenesis and angiogenesis. The expression of ephrin A1 was two and three to nine times higher than that of the draining vein and normal brain, respectively, using real-time reverse transcription-polymerase chain reaction. For the first time, here we report the increased expression of ephrin A1 in brain AVM, which may play an important role in the pathogenesis of AVM.