Coexpression of Angiogenic Factors in Brain Arteriovenous Malformations

Abstract

Brain arteriovenous malformations (BAVMs) are structurally unstable blood vessels that display an angiogenic phenotype, possibly maintained by concerted effects of key angiogenic factors. Therefore, we hypothesized that there are close correlations among key angiogenic factors in BAVMs and that levels of key angiogenic factors are associated with BAVM clinical characteristics that are linked with vascular instability. We measured the expression of angiopoietin-2 (Ang-2), matrix metalloproteinase-9, vascular endothelial growth factor (VEGF), and platelet-derived growth factor-AA and -BB by use of enzyme-linked immunosorbent assay in 27 BAVM surgical specimens. Tissues were also collected from 14 structurally normal brain specimens obtained during epilepsy surgery. Ang-2, VEGF, and matrix metalloproteinase-9 were highly expressed in BAVM samples (11.9 +/- 15.5 ng/mg protein, 137 +/- 102 pg/mg protein, and 379 +/- 455 pg/mg protein, respectively). Platelet-derived growth factor-BB was detectable in 7 of 21 BAVM samples. There were close correlations between Ang-2 and VEGF (R2 = 0.79). Higher Ang-2 and VEGF levels seemed to be associated with draining vein characteristics linked with BAVM hemorrhage but not with feeding artery pressure or BAVM size. In the structurally normal brain specimens, levels of Ang-2, VEGF, and matrix metalloproteinase-9 were low (0.8 +/- 2.3 ng/mg protein, 38 +/- 25 pg/mg protein, and 52 +/- 43 pg/mg protein, respectively). There were close correlations among angiogenic factors in BAVMs. Concerted effects of angiogenic factors may maintain the angiogenic phenotype in BAVMs and thereby determine the clinical course of BAVMs.