Abnormal expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in brain arteriovenous malformations.
OBJECTIVE
Excessive degradation of the vascular matrix by matrix metalloproteinases (MMPs) can lead to structural instability of vessels. In this study we examined the expression of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in brain arteriovenous malformations (BAVMs).


METHODS
We performed gelatin zymography for MMPs and Western blot for MMP-9, MMP-2, TIMP-1, TIMP-2, TIMP-3, and TIMP-4. MMP-9 expression was localized by immunohistochemistry.


RESULTS
We analyzed 37 BAVM specimens and 9 control brain specimens from epilepsy surgery. Thirty-two BAVM patients had embolization treatment before resection. Eighteen BAVM patients had a history of hemorrhage from BAVMs. Neither MMP-2 nor TIMP-2 was detected in BAVMs or control brain specimens. Compared with control brain samples, BAVM samples had higher levels of total MMP-9, active MMP-9, pro-MMP-9, TIMP-1, and TIMP-3. TIMP-4 levels were higher in the control brain than in BAVM specimens. MMP-9 was localized to the endothelial cell/peri-endothelial cell layer and infiltrating neutrophils of BAVMs. BAVMs with venous stenosis >or=50% had higher expression of MMP-9 than BAVMs with venous stenosis <50%. There was no apparent association between total MMP-9, pro-MMP-9, or active MMP-9 levels and (1) feeding artery pressure, (2) pattern of draining vein (exclusively deep venous drainage versus any superficial drainage), and (3) BAVM size.


CONCLUSIONS
We found increased levels of MMP-9 and TIMPs in BAVMs. Abnormal balance of MMP-9 and TIMPs may contribute to vascular instability of BAVMs.
Hashimoto
Tomoki
T
Department of Anesthesia and Perioperative Care, University of California, San Francisco 94110, USA.
Wen
Gen
G
Lawton
Michael T
MT
Boudreau
Nancy J
NJ
Bollen
Andrew W
AW
Yang
Guo-Yuan
GY
Barbaro
Nicholas M
NM
Higashida
Randall T
RT
Dowd
Christopher F
CF
Halbach
Van V
VV
Young
William L
WL
D000328:Adult; D001921:Brain / Q000201:enzymology; D004621:Embolization, Therapeutic; D005260:Female; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000175:diagnosis / Q000201:enzymology* / Q000628:therapy; D020300:Intracranial Hemorrhages / Q000175:diagnosis; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019714:Tissue Inhibitor of Metalloproteinases; D017493:Leukocyte Common Antigens; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9