Adenovirus-mediated gene transfer of the human tissue inhibitor of metalloproteinase-2 blocks vascular smooth muscle cell invasiveness in vitro and modulates neointimal development in vivo

Linda Cheng, Giuditta Mantile, Rebecca Pauly, Cynthia Nater, Angelina Felici, Robert Monticone, Claudio Bilato, Yehezkiel A. Gluzband, Michael T. Crow, William Stetler-Stevenson, Maurizio C. Capogrossi

Research output: Contribution to journalArticle

Abstract

Background - Endovascular injury induced by balloon withdrawal leads to the increased activation of matrix metalloproteinases (MMPs) in the vascular wall, allowing smooth muscle cells (SMCs) to digest the surrounding extracellular matrix (ECM) and migrate from the media into the intima. The objective of this study was to examine the effects of a replication-deficient adenovirus carrying the cDNA for human tissue inhibitor of metalloproteinase- 2 (AdCMV.hTIMP-2) on SMC function in vitro and neointimal development in the injured rat carotid artery. Methods and Results - Infection of cultured rat aortic SMCs at a multiplicity of infection of 100 with AdCMV.hTIMP-2 resulted in high-level expression of hTIMP-2 mRNA and protein secretion into the medium. Conditioned media (CM) from AdCMV.hTIMP-2-infected but not control virus (AdCMV.null or AdCMV.βgal)-infected SMCs inhibited MMP-2 activity on gelatin zymograms as well as the chemoattractant-directed migration of SMCs across reconstituted basement membrane proteins in the Boyden chamber assay. In contrast, AdCMV.hTIMP-2 CM had no effect on chemoattractant-directed migration of SMCs occurring in the absence of an ECM barrier or on the proliferation of cultured neointimal SMCs. Delivery of AdCMV.hTIMP-2 (2.5 X 109 pfu) to the carotid artery wall at the time of balloon withdrawal injury inhibited SMC migration into the intima by 36% (P

Original languageEnglish (US)
Pages (from-to)2195-2201
Number of pages7
JournalCirculation
Volume98
Issue number20
StatePublished - Nov 17 1998
Externally publishedYes

Fingerprint

Vascular Smooth Muscle
Adenoviridae
Smooth Muscle Myocytes
Genes
Chemotactic Factors
Conditioned Culture Medium
Carotid Arteries
Extracellular Matrix
In Vitro Techniques
human TIMP2 protein
Matrix Metalloproteinase 2
Wounds and Injuries
Gelatin
Infection
Matrix Metalloproteinases
Basement Membrane
Cell Movement
Blood Vessels
Membrane Proteins
Complementary DNA

Keywords

  • Genes
  • Metalloproteinases
  • Restenosis
  • Viruses

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Adenovirus-mediated gene transfer of the human tissue inhibitor of metalloproteinase-2 blocks vascular smooth muscle cell invasiveness in vitro and modulates neointimal development in vivo. / Cheng, Linda; Mantile, Giuditta; Pauly, Rebecca; Nater, Cynthia; Felici, Angelina; Monticone, Robert; Bilato, Claudio; Gluzband, Yehezkiel A.; Crow, Michael T.; Stetler-Stevenson, William; Capogrossi, Maurizio C.

In: Circulation, Vol. 98, No. 20, 17.11.1998, p. 2195-2201.

Research output: Contribution to journalArticle

Cheng, L, Mantile, G, Pauly, R, Nater, C, Felici, A, Monticone, R, Bilato, C, Gluzband, YA, Crow, MT, Stetler-Stevenson, W & Capogrossi, MC 1998, 'Adenovirus-mediated gene transfer of the human tissue inhibitor of metalloproteinase-2 blocks vascular smooth muscle cell invasiveness in vitro and modulates neointimal development in vivo', Circulation, vol. 98, no. 20, pp. 2195-2201.
Cheng, Linda ; Mantile, Giuditta ; Pauly, Rebecca ; Nater, Cynthia ; Felici, Angelina ; Monticone, Robert ; Bilato, Claudio ; Gluzband, Yehezkiel A. ; Crow, Michael T. ; Stetler-Stevenson, William ; Capogrossi, Maurizio C. / Adenovirus-mediated gene transfer of the human tissue inhibitor of metalloproteinase-2 blocks vascular smooth muscle cell invasiveness in vitro and modulates neointimal development in vivo. In: Circulation. 1998 ; Vol. 98, No. 20. pp. 2195-2201.
@article{bb4e024681f14db580ee6830370d6461,
title = "Adenovirus-mediated gene transfer of the human tissue inhibitor of metalloproteinase-2 blocks vascular smooth muscle cell invasiveness in vitro and modulates neointimal development in vivo",
abstract = "Background - Endovascular injury induced by balloon withdrawal leads to the increased activation of matrix metalloproteinases (MMPs) in the vascular wall, allowing smooth muscle cells (SMCs) to digest the surrounding extracellular matrix (ECM) and migrate from the media into the intima. The objective of this study was to examine the effects of a replication-deficient adenovirus carrying the cDNA for human tissue inhibitor of metalloproteinase- 2 (AdCMV.hTIMP-2) on SMC function in vitro and neointimal development in the injured rat carotid artery. Methods and Results - Infection of cultured rat aortic SMCs at a multiplicity of infection of 100 with AdCMV.hTIMP-2 resulted in high-level expression of hTIMP-2 mRNA and protein secretion into the medium. Conditioned media (CM) from AdCMV.hTIMP-2-infected but not control virus (AdCMV.null or AdCMV.βgal)-infected SMCs inhibited MMP-2 activity on gelatin zymograms as well as the chemoattractant-directed migration of SMCs across reconstituted basement membrane proteins in the Boyden chamber assay. In contrast, AdCMV.hTIMP-2 CM had no effect on chemoattractant-directed migration of SMCs occurring in the absence of an ECM barrier or on the proliferation of cultured neointimal SMCs. Delivery of AdCMV.hTIMP-2 (2.5 X 109 pfu) to the carotid artery wall at the time of balloon withdrawal injury inhibited SMC migration into the intima by 36{\%} (P",
keywords = "Genes, Metalloproteinases, Restenosis, Viruses",
author = "Linda Cheng and Giuditta Mantile and Rebecca Pauly and Cynthia Nater and Angelina Felici and Robert Monticone and Claudio Bilato and Gluzband, {Yehezkiel A.} and Crow, {Michael T.} and William Stetler-Stevenson and Capogrossi, {Maurizio C.}",
year = "1998",
month = "11",
day = "17",
language = "English (US)",
volume = "98",
pages = "2195--2201",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "20",

}

TY - JOUR

T1 - Adenovirus-mediated gene transfer of the human tissue inhibitor of metalloproteinase-2 blocks vascular smooth muscle cell invasiveness in vitro and modulates neointimal development in vivo

AU - Cheng, Linda

AU - Mantile, Giuditta

AU - Pauly, Rebecca

AU - Nater, Cynthia

AU - Felici, Angelina

AU - Monticone, Robert

AU - Bilato, Claudio

AU - Gluzband, Yehezkiel A.

AU - Crow, Michael T.

AU - Stetler-Stevenson, William

AU - Capogrossi, Maurizio C.

PY - 1998/11/17

Y1 - 1998/11/17

N2 - Background - Endovascular injury induced by balloon withdrawal leads to the increased activation of matrix metalloproteinases (MMPs) in the vascular wall, allowing smooth muscle cells (SMCs) to digest the surrounding extracellular matrix (ECM) and migrate from the media into the intima. The objective of this study was to examine the effects of a replication-deficient adenovirus carrying the cDNA for human tissue inhibitor of metalloproteinase- 2 (AdCMV.hTIMP-2) on SMC function in vitro and neointimal development in the injured rat carotid artery. Methods and Results - Infection of cultured rat aortic SMCs at a multiplicity of infection of 100 with AdCMV.hTIMP-2 resulted in high-level expression of hTIMP-2 mRNA and protein secretion into the medium. Conditioned media (CM) from AdCMV.hTIMP-2-infected but not control virus (AdCMV.null or AdCMV.βgal)-infected SMCs inhibited MMP-2 activity on gelatin zymograms as well as the chemoattractant-directed migration of SMCs across reconstituted basement membrane proteins in the Boyden chamber assay. In contrast, AdCMV.hTIMP-2 CM had no effect on chemoattractant-directed migration of SMCs occurring in the absence of an ECM barrier or on the proliferation of cultured neointimal SMCs. Delivery of AdCMV.hTIMP-2 (2.5 X 109 pfu) to the carotid artery wall at the time of balloon withdrawal injury inhibited SMC migration into the intima by 36% (P

AB - Background - Endovascular injury induced by balloon withdrawal leads to the increased activation of matrix metalloproteinases (MMPs) in the vascular wall, allowing smooth muscle cells (SMCs) to digest the surrounding extracellular matrix (ECM) and migrate from the media into the intima. The objective of this study was to examine the effects of a replication-deficient adenovirus carrying the cDNA for human tissue inhibitor of metalloproteinase- 2 (AdCMV.hTIMP-2) on SMC function in vitro and neointimal development in the injured rat carotid artery. Methods and Results - Infection of cultured rat aortic SMCs at a multiplicity of infection of 100 with AdCMV.hTIMP-2 resulted in high-level expression of hTIMP-2 mRNA and protein secretion into the medium. Conditioned media (CM) from AdCMV.hTIMP-2-infected but not control virus (AdCMV.null or AdCMV.βgal)-infected SMCs inhibited MMP-2 activity on gelatin zymograms as well as the chemoattractant-directed migration of SMCs across reconstituted basement membrane proteins in the Boyden chamber assay. In contrast, AdCMV.hTIMP-2 CM had no effect on chemoattractant-directed migration of SMCs occurring in the absence of an ECM barrier or on the proliferation of cultured neointimal SMCs. Delivery of AdCMV.hTIMP-2 (2.5 X 109 pfu) to the carotid artery wall at the time of balloon withdrawal injury inhibited SMC migration into the intima by 36% (P

KW - Genes

KW - Metalloproteinases

KW - Restenosis

KW - Viruses

UR - http://www.scopus.com/inward/record.url?scp=0032542035&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032542035&partnerID=8YFLogxK

M3 - Article

C2 - 9815875

AN - SCOPUS:0032542035

VL - 98

SP - 2195

EP - 2201

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 20

ER -