title: Increased expression of membrane-type matrix metalloproteinase and preferential localization of matrix metalloproteinase-2 to the neointima of balloon-injured rat carotid arteries.
abstract: 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.
  
  
  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.
authors.affiliation: Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Md 21224, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Jenkins
authors.forename: M T
authors.initials: MT
authors.lastname: Crow
authors.forename: C
authors.initials: C
authors.lastname: Bilato
authors.forename: Y
authors.initials: Y
authors.lastname: Gluzband
authors.forename: W S
authors.initials: WS
authors.lastname: Ryu
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Stetler-Stevenson
authors.forename: C
authors.initials: C
authors.lastname: Nater
authors.forename: J P
authors.initials: JP
authors.lastname: Froehlich
authors.forename: E G
authors.initials: EG
authors.lastname: Lakatta
authors.forename: L
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D015153:Blotting, Western; D002339:Carotid Arteries / Q000201:enzymology* / Q000473:pathology*; D020212:Carotid Artery Injuries; D018093:Gelatinases / Q000032:analysis*; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017539:Tunica Intima / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D018093:Gelatinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2