Matrix metalloproteinase-9 may play a role in recanalization and recurrence after therapeutic embolization of aneurysms or arteries.

PURPOSE

Matrix metalloproteinase (MMP)-9 plays various roles in vascular healing and angiogenesis. This study was conducted to determine if MMP-9 is involved in healing or recanalization after therapeutic occlusion of arteries or aneurysms.

MATERIALS AND METHODS

Angiographic and pathologic changes were investigated in canine bilateral venous pouch carotid aneurysms embolized with gelatin sponges with or without previous endothelial denudation, a procedure that can prevent recanalization. To assess a potential role of MMP-9, messenger RNA (mRNA) and protein were compared in denuded and nondenuded aneurysms 4, 7, and 14 days after embolization. To assess if MMP-9 is essential to arterial recanalization, transmyocardial angiography and pathologic findings were compared 14 days after carotid occlusion with platinum coils in MMP-9-knockout and wild-type mice.

RESULTS

Denudation of the endothelial lining led to improved angiographic results at 3 weeks (P < .001). Neointimal closure of the aneurysm neck was more complete in denuded versus nondenuded aneurysms. Denudation was followed by a decrease in MMP-9 mRNA (86%, P < .05) and protein (30%, P < .05) 7 days after embolization and a decrease in von Willebrand factor compared with nondenuded aneurysms. MMP-9 immunostaining of axial sections from embolized aneurysms confirmed MMP-9-positive endothelialized clefts, which were absent in denuded aneurysms. Transmyocardial angiography and pathologic examination showed recanalization of one of nine coiled carotid arteries of MMP-9-knockout mice, compared with five of seven controls (P = .035).

CONCLUSIONS

MMP-9 may play a role in recanalization of arteries after coil occlusion and in recurrences after sponge embolization of aneurysms.