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 (R2=.76, P<.001), as well as with IL-6 (R2=.32, P<.001). In contrast, MMP-9 in BAVM poorly correlated with the endothelial marker, eNOS (R2=.03, P=.05), and CD31 (R2=.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.
- Matrix metalloprotease-9
- Vascular Malformations
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)