MMP-9 expression is associated with leukocytic but not endothelial markers in brain arteriovenous malformations

Brain arteriovenous malformations (BAVM) have high matrix metalloproteinase-9 (MMP-9) expression, the source of which is unclear. We hypothesized MMP-9 production might be due to inflammation in BAVM. Compared to control brain tissues (n=5), BAVM tissue (n=139) had a higher expression (by ELISA) of myeloperoxidase (MPO) (193 +/- 189 vs. 6 +/- 3, ng/mg, P <.001), MMP-9 (28 +/- 32 vs. 0.7 +/- 0.6, ng/mg, P <.001), and IL-6 (102 +/- 218 vs. 0.1 +/- 0.1, pg/mg, P <.001), but not eNOS (114 +/- 87 vs. 65 +/- 9, pg/mg, P=.09). MMP-9 expression in BAVM highly correlated with myeloperoxidase (R-2=.76, P <.001), as well as with IL-6 (R-2=.32, P <.001). In contrast, MMP-9 in BAVM poorly correlated with the endothelial marker, eNOS (R-2=.03, P=.05), and CD31 (R-2=.004, P=.57). Compared to non-embolized patients (n=46), patients with pre-operative embolization (n=93) had higher levels of myeloperoxidase (236 +/- 205 vs. 106 +/- 108, ng/mg, P <.001) and MMP-9 (33 +/- 35 vs. 16 +/- 20, ng/mg, P <.001), however the correlation between MMP-9 and myeloperoxidase was equally strong for both groups (R-2=.69, n=93, P <.001, for both). MMP-9 expression correlated with the lipocalin-MMP-9 complex, suggesting neutrophils as the MMP-9 source. MPO co-localized with majority of MMP-9 signal by immunohistochemistry. Our data suggest that inflammation is a prominent feature of BAVM lesional phenotype, and neutrophils appear to be a major source of MMP-9 in these lesions.