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 (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 (R2 = .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.
Chen
Yongmei
Y
Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94110, USA.
Fan
Yongfeng
Y
Poon
K Y Trudy
KY
Achrol
Achal S
AS
Lawton
Michael T
MT
Zhu
Yiqian
Y
McCulloch
Charles E
CE
Hashimoto
Tomoki
T
Lee
Chanhung
C
Barbaro
Nicholas M
NM
Bollen
Andrew W
AW
Yang
Guo-Yuan
GY
Young
William L
WL
D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D004621:Embolization, Therapeutic; D042783:Endothelial Cells / Q000201:enzymology; D005260:Female; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D002538:Intracranial Arteriovenous Malformations / Q000201:enzymology* / Q000276:immunology / Q000628:therapy; D007962:Leukocytes / Q000201:enzymology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D009504:Neutrophils / Q000201:enzymology; D052250:Nitric Oxide Synthase Type III / Q000032:analysis / Q000096:biosynthesis; D009195:Peroxidase / Q000032:analysis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000096:biosynthesis; D011446:Prospective Studies
D015415:Biomarkers; D015850:Interleukin-6; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D009195:Peroxidase; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D020780:Matrix Metalloproteinase 9