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 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 - 1998
Externally publishedYes

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Membrane-Associated Matrix Metalloproteinases
Neointima
Matrix Metalloproteinase 2
Matrix Metalloproteinases
Carotid Arteries
Matrix Metalloproteinase 14
Tissue Inhibitor of Metalloproteinase-2
Wounds and Injuries
Gelatin
Western Blotting
Vascular System Injuries
Metalloproteases
Vascular Smooth Muscle
Smooth Muscle Myocytes
Extracellular Matrix

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Increased expression of membrane-type matrix metalloproteinase and preferential localization of matrix metalloproteinase-2 to the neointima of balloon-injured rat carotid arteries. / Mark Jenkins, G.; Crow, Michael T.; Bilato, Claudio; Gluzband, Yehezkiel; Ryu, Wang Seong; Li, Zhihe; Stetler-Stevenson, William; Nater, Cynthia; Froehlich, Jeffrey P.; Lakatta, Edward; Cheng, Linda.

In: Circulation, Vol. 97, No. 1, 1998, p. 82-90.

Research output: Contribution to journalArticle

Mark Jenkins, G, Crow, MT, Bilato, C, Gluzband, Y, Ryu, WS, Li, Z, Stetler-Stevenson, W, Nater, C, Froehlich, JP, Lakatta, E & 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, vol. 97, no. 1, pp. 82-90.
Mark Jenkins, G. ; Crow, Michael T. ; Bilato, Claudio ; Gluzband, Yehezkiel ; Ryu, Wang Seong ; Li, Zhihe ; Stetler-Stevenson, William ; Nater, Cynthia ; Froehlich, Jeffrey P. ; Lakatta, Edward ; Cheng, Linda. / Increased expression of membrane-type matrix metalloproteinase and preferential localization of matrix metalloproteinase-2 to the neointima of balloon-injured rat carotid arteries. In: Circulation. 1998 ; Vol. 97, No. 1. pp. 82-90.
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AU - Crow, Michael T.

AU - Bilato, Claudio

AU - Gluzband, Yehezkiel

AU - Ryu, Wang Seong

AU - Li, Zhihe

AU - Stetler-Stevenson, William

AU - Nater, Cynthia

AU - Froehlich, Jeffrey P.

AU - Lakatta, Edward

AU - Cheng, Linda

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AB - 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.

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