Matrix metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury.
Matrix metalloproteinases (MMPs) and, in particular, MMP-9 are important for smooth muscle cell (SMC) migration into the intima. In this study, we sought to determine whether MMP-9 is critical for SMC migration and for the formation of a neointima by using mice in which the gene was deleted (MMP-9(-/-) mice). A denuding injury to the arteries of wild-type mice promoted the migration of medial SMCs into the neointima at 6 days, and a large neointimal lesion was observed after 28 days. In wild-type arteries, medial SMC replication was approximately 8% at day 4, 6% at day 6, and 4% at day 8 and had further decreased to 1% at day 14. Intimal cell replication was 65% at 8 days and had decreased to approximately 10% at 14 days after injury. In MMP-9(-/-) arteries, SMC replication was significantly lower at day 8. In addition, SMC migration and arterial lesion growth were significantly impaired in MMP-9(-/-) arteries. SMCs, isolated from MMP-9(-/-) mouse arteries, showed an impairment of migration and replication in vitro. Thus, our present data indicate that MMP-9 is critical for the development of arterial lesions by regulating both SMC migration and proliferation.
Cho
Aesim
A
Department of Pathology, University of Washington, Seattle 98026, USA. ascho@u.washington.edu
Reidy
Michael A
MA
D000818:Animals; D002339:Carotid Arteries / Q000201:enzymology* / Q000473:pathology; D016893:Carotid Stenosis / Q000201:enzymology / Q000209:etiology / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects; D002452:Cell Count; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D004789:Enzyme Activation; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D017539:Tunica Intima / Q000201:enzymology / Q000293:injuries* / Q000473:pathology
D020780:Matrix Metalloproteinase 9