Abnormal expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in brain arteriovenous malformations

Document Type

Article

Abstract

BACKGROUND AND PURPOSE: 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.

Medical Subject Headings

Adult; Brain (enzymology); Embolization, Therapeutic; Female; Humans; Intracranial Arteriovenous Malformations (diagnosis, enzymology, therapy); Intracranial Hemorrhages (diagnosis); Leukocyte Common Antigens (metabolism); Male; Matrix Metalloproteinase 9 (metabolism); Matrix Metalloproteinases (metabolism); Platelet Endothelial Cell Adhesion Molecule-1 (metabolism); Tissue Inhibitor of Metalloproteinases (metabolism)

Publication Date

3-22-2003

Publication Title

Stroke

E-ISSN

1524-4628

Volume

34

Issue

4

First Page

925

Last Page

31

PubMed ID

12649522

Digital Object Identifier (DOI)

10.1161/01.STR.0000061888.71524.DF

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