Increased expression of membrane-type matrix metalloproteinase and preferential localization of matrix metalloproteinase-2 to the neointima of balloon-injured rat carotid arteries.
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.
Jenkins
G M
GM
Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Md 21224, USA.
Crow
M T
MT
Bilato
C
C
Gluzband
Y
Y
Ryu
W S
WS
Li
Z
Z
Stetler-Stevenson
W
W
Nater
C
C
Froehlich
J P
JP
Lakatta
E G
EG
Cheng
L
L
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*
D012333:RNA, Messenger; D018093:Gelatinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2