Suppression of MMP-9 by doxycycline in brain arteriovenous malformations.
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 microg/ml significantly decreased MMP-9 levels in AVM tissues ex-vivo (total: control vs 10 vs 100 microg/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 microg 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.
Hashimoto
Tomoki
T
Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, San Francisco, California, USA. hashimot@anesthesia.ucsf.edu
Matsumoto
Melissa M
MM
Li
Jenny F
JF
Lawton
Michael T
MT
Young
William L
WL
D000328:Adult; D002478:Cells, Cultured; D004318:Doxycycline / Q000494:pharmacology*; D005240:Feasibility Studies; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000188:drug therapy* / Q000201:enzymology* / Q000601:surgery; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D010865:Pilot Projects
D061965:Matrix Metalloproteinase Inhibitors; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline