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Circulation Research. 2002;91:845-851
Published online before print October 3, 2002, doi: 10.1161/01.RES.0000040420.17366.2E
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Right arrow Genetically altered mice
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(Circulation Research. 2002;91:845.)
© 2002 American Heart Association, Inc.


Integrative Physiology

Matrix Metalloproteinase-9 Is Necessary for the Regulation of Smooth Muscle Cell Replication and Migration After Arterial Injury

Aesim Cho, Michael A. Reidy

From the Department of Pathology, University of Washington, Seattle.

Correspondence to Aesim Cho, PhD, Department of Pathology, Box 357335, University of Washington, 1959 NE Pacific St, Seattle, WA 98026. E-mail ascho{at}u.washington.edu

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 {approx}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 {approx}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.


Key Words: matrix metalloproteinase-9 • mouse arterial injury • smooth muscle cell replication • migration • neointimal formation




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