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Suppression of MMP-9 by doxycycline in brain arteriovenous malformations

2005; BioMed Central; Volume: 5; Issue: 1 Linguagem: Inglês

10.1186/1471-2377-5-1

1471-2377

Tomoki Hashimoto, Melissa Matsumoto, Jenny F Li, Michael T. Lawton, William L. Young,

Moyamoya disease diagnosis and treatment

Abstract Background The primary aim of this study is to demonstrate the feasibility of utilizing doxycycline to suppress matrix metalloproteinase-9 (MMP-9) in brain arteriovenous malformations (AVMs). Methods Ex-vivo treatment of AVM tissues: Intact AVM tissues were treated with doxycycline for 48 hours. Active and total MMP-9 in the medium were measured. Pilot trial: AVM patients received either doxycycline (100 mg) or placebo twice a day for one week prior to AVM resection. Active and total MMP-9 in BVM tissues were measured. Results Ex-vivo treatment of AVM tissues: Doxycycline at 10 and 100 μg/ml significantly decreased MMP-9 levels in AVM tissues ex-vivo (total: control vs 10 vs 100 μg/ml = 100 ± 6 vs 60 ± 16 vs 61 ± 9%; active: 100 ± 8 vs 48 ± 16 vs 59 ± 10%). Pilot trial: 10 patients received doxycycline, and 4 patients received placebo. There was a trend for both MMP-9 levels to be lower in the doxycycline group than in the placebo group (total: 2.18 ± 1.94 vs 3.26 ± 3.58, P = .50; active: 0.48 ± 0.48 vs 0.95 ± 1.01 ng/100 μg protein, P = .25). Conclusions A clinically relevant concentration of doxycycline decreased MMP-9 in ex-vivo AVM tissues. Furthermore, there was a trend that oral doxycycline for as short as one week resulted in a decrease in MMP-9 in AVM tissues. Further studies are warranted to justify a clinical trial to test effects of doxycycline on MMP-9 expression in AVM tissues.