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

Yongmei Chen, Yongfeng Fan, K. Y.Trudy Poon, Achal S. Achrol, Michael T. Lawton, Yiqian Zhu, Charles E. McCulloch, Tomoki Hashimoto, Chanhung Lee, Nicholas M. Barbaro, Andrew W. Bollen, Guo Yuan Yang, William L. Young

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3121-3128
Number of pages8
JournalFrontiers in Bioscience
Volume11
Issue numberSUPPL. 3
DOIs
StatePublished - 2006

Keywords

  • Brain
  • Inflammation
  • Matrix metalloprotease-9
  • Myeloperoxidase
  • Vascular Malformations

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Chen, Y., Fan, Y., Poon, K. Y. T., Achrol, A. S., Lawton, M. T., Zhu, Y., McCulloch, C. E., Hashimoto, T., Lee, C., Barbaro, N. M., Bollen, A. W., Yang, G. Y., & Young, W. L. (2006). MMP-9 expression is associated with leukocytic but not endothelial markers in brain arteriovenous malformations. Frontiers in Bioscience, 11(SUPPL. 3), 3121-3128. https://doi.org/10.2741/2037