Increased expression of membrane-type matrix metalloproteinase and preferential localization of matrix metalloproteinase-2 to the neointima of balloon-injured rat carotid arteries

G. Mark Jenkins, Michael T. Crow, Claudio Bilato, Yehezkiel Gluzband, Wang Seong Ryu, Zhihe Li, William Stetler-Stevenson, Cynthia Nater, Jeffrey P. Froehlich, Edward G. Lakatta, Linda Cheng

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish (US)
Pages (from-to)82-90
Number of pages9
JournalCirculation
Volume97
Issue number1
StatePublished - Jan 26 1998

Keywords

  • Carotid arteries
  • Extracellular matrix
  • Metalloproteinases
  • Neointima
  • Restenosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Mark Jenkins, G., Crow, M. T., Bilato, C., Gluzband, Y., Ryu, W. S., Li, Z., Stetler-Stevenson, W., Nater, C., Froehlich, J. P., Lakatta, E. G., & Cheng, L. (1998). Increased expression of membrane-type matrix metalloproteinase and preferential localization of matrix metalloproteinase-2 to the neointima of balloon-injured rat carotid arteries. Circulation, 97(1), 82-90.