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From the Laboratory of Cardiovascular Science, National Institute on
Aging, National Institutes of Health, Baltimore, Md; and the Laboratory of
Pathology (W.S.-S.), National Cancer Institute, National Institutes on Aging,
Bethesda, Md.
Correspondence to Michael T. Crow, PhD, Laboratory of Cardiovascular Science, National Institute on Aging-NIH, Gerontology Research Center, 4940 Eastern Ave, Baltimore, MD 21224. E-mail CROWM{at}GRC.NIA.NIH.GOV
Background—Remodeling of the injured
vascular wall is dependent on the action of several extracellular
proteases. Previous studies have shown that expression of matrix
metalloproteinases (MMP-2 and MMP-9) is upregulated after vascular
injury and that MMP-2 is required for the migration of cultured
vascular smooth muscle cells across complex extracellular matrix
barriers. The present study examined changes in the expression of
membrane-type metalloproteinase (MT–MMP-1), a putative regulator of
MMP-2, in the tissue localization of MMP-2, and in the expression of
activated and latent forms of MMP-2 and the tissue
inhibitor of metalloproteinases, TIMP-2, in rat carotid
arteries subjected to balloon catheter injury.
Methods and Results—MT–MMP-1 mRNA levels increased sixfold after
3 days of injury, coinciding with an increase in MMP-2 activation
assessed by gelatin zymography. Western blotting and gelatin zymography
showed an increase in MMP-2 protein levels beginning 5 to 7 days after
injury; immunocytochemistry and Western blotting showed that the
increase occurred preferentially in the developing
neointima.
Conclusions—These results show that increased expression of
MT–MMP-1 and activation of MMP-2 occurs early after injury to the rat
carotid artery and that at later times MMP-2 is preferentially
localized to the developing neointima.
© 1998 American Heart Association, Inc.
Basic Science Reports
Increased Expression of Membrane-Type Matrix Metalloproteinase and Preferential Localization of Matrix Metalloproteinase-2 to the Neointima of Balloon-Injured Rat Carotid Arteries
Key Words: restenosis • neointima • extracellular matrix • metalloproteinases • carotid arteries
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