INCREASED EXPRESSION OF MEMBRANE-TYPE MATRIX METALLOPROTEINASE AND PREFERENTIAL LOCALIZATION OF MATRIX METALLOPROTEINASE-2 TO THE NEOINTIMAOF BALLOON-INJURED RAT CAROTID ARTERIES

Background-Remodeling of the injured vascular wall is dependent on the action of several extracellular proteases. Previous studies have show n that expression of matrix metalloproteinases (MMP-2 and MMP-9) is up regulated after vascular injury and that MMP-2 is required for the mig ration of cultured vascular smooth muscle cells across complex extrace llular matrix barriers. The present study examined changes ill the exp ression of membrane-type metalloproteinase (MT-MMP-1), a putative regu lator of MMP-2, in the tissue localization of MMP-2, and in the expres sion of activated and latent forms of MMP-2 and the tissue inhibitor o f metalloproteinases, TIMP-2, in rat carotid arteries subjected to bal loon catheter injury. Methods and Results-MT-MMP-1 mRNA levels increas ed sixfold after 3 days of injury, coinciding with an increase in MMP- 2 activation assessed by gelatin zymography. Western blotting and gela tin zymography showed an increase in MMP-2 protein levels beginning 5 to 7 days after injury; immunocytochemistry and Western blotting showe d that the increase occurred preferentially in the developing neointim a. 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 t he developing neointima.