Direct transfer of transforming growth factor β1 gene into arteries stimulates fibrocellular hyperplasia

E. G. Nabel, L. Shum, V. J. Pompili, Z. Y. Yang, H. San, Bing Shu Hong Bing Shu, S. Liptay, L. Gold, D. Gordon, R. Derynck, G. J. Nabel

Research output: Contribution to journalArticle

324 Citations (Scopus)

Abstract

The arterial wall responds to thrombosis or mechanical injury through the induction of specific gene products that increase cellular proliferation and connective tissue formation. These changes result in intimal hyperplasia that is observed in restenosis and the early phases of atherosclerosis. Transforming growth factor β1 (TGF-β1) is a secreted multi-functional protein that plays an important role in embryonal development and in repair following tissue injury. However, the function of TGF-β1 in vascular cell growth in vivo has not been defined. In this report, we have evaluated the role of TGF-β1 in the pathophysiology of intimal and medial hyperplasia by gene transfer of an expression plasmid encoding active TGF-β1 into porcine arteries. Expression of TGF-β1 in normal arteries resulted in substantial extracellular matrix production accompanied by intimal and medial hyperplasia. Increased procollagen, collagen, and proteoglycan synthesis in the neointima was demonstrated by immunohistochemistry relative to control transfected arteries. Expression of TGF-β1 induced a distinctly different program of gene expression and biologic response from the platelet-derived growth factor B (PDGF B) gene: procollagen synthesis induced by TGF-β1 was greater, and cellular proliferation was less prominent. These findings show that TGF-β1 differentially modulates extracellular matrix production and cellular proliferation in the arterial wall in vivo and could play a reparative role in the response to arterial injury.

Original languageEnglish (US)
Pages (from-to)10759-10763
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number22
DOIs
StatePublished - Nov 30 1993

Fingerprint

Transforming Growth Factors
Hyperplasia
Arteries
Tunica Intima
Genes
Procollagen
Cell Proliferation
Extracellular Matrix
Wounds and Injuries
Proto-Oncogene Proteins c-sis
Gene Expression
Neointima
Proteoglycans
Connective Tissue
Blood Vessels
Atherosclerosis
Thrombosis
Plasmids
Swine
Collagen

Keywords

  • cellular proliferation
  • extracellular matrix
  • gene expression
  • gene transfer

ASJC Scopus subject areas

  • General

Cite this

Direct transfer of transforming growth factor β1 gene into arteries stimulates fibrocellular hyperplasia. / Nabel, E. G.; Shum, L.; Pompili, V. J.; Yang, Z. Y.; San, H.; Hong Bing Shu, Bing Shu; Liptay, S.; Gold, L.; Gordon, D.; Derynck, R.; Nabel, G. J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 22, 30.11.1993, p. 10759-10763.

Research output: Contribution to journalArticle

Nabel, EG, Shum, L, Pompili, VJ, Yang, ZY, San, H, Hong Bing Shu, BS, Liptay, S, Gold, L, Gordon, D, Derynck, R & Nabel, GJ 1993, 'Direct transfer of transforming growth factor β1 gene into arteries stimulates fibrocellular hyperplasia', Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 22, pp. 10759-10763. https://doi.org/10.1073/pnas.90.22.10759
Nabel, E. G. ; Shum, L. ; Pompili, V. J. ; Yang, Z. Y. ; San, H. ; Hong Bing Shu, Bing Shu ; Liptay, S. ; Gold, L. ; Gordon, D. ; Derynck, R. ; Nabel, G. J. / Direct transfer of transforming growth factor β1 gene into arteries stimulates fibrocellular hyperplasia. In: Proceedings of the National Academy of Sciences of the United States of America. 1993 ; Vol. 90, No. 22. pp. 10759-10763.
@article{c4d173654129470a8e3a2596ce1c9027,
title = "Direct transfer of transforming growth factor β1 gene into arteries stimulates fibrocellular hyperplasia",
abstract = "The arterial wall responds to thrombosis or mechanical injury through the induction of specific gene products that increase cellular proliferation and connective tissue formation. These changes result in intimal hyperplasia that is observed in restenosis and the early phases of atherosclerosis. Transforming growth factor β1 (TGF-β1) is a secreted multi-functional protein that plays an important role in embryonal development and in repair following tissue injury. However, the function of TGF-β1 in vascular cell growth in vivo has not been defined. In this report, we have evaluated the role of TGF-β1 in the pathophysiology of intimal and medial hyperplasia by gene transfer of an expression plasmid encoding active TGF-β1 into porcine arteries. Expression of TGF-β1 in normal arteries resulted in substantial extracellular matrix production accompanied by intimal and medial hyperplasia. Increased procollagen, collagen, and proteoglycan synthesis in the neointima was demonstrated by immunohistochemistry relative to control transfected arteries. Expression of TGF-β1 induced a distinctly different program of gene expression and biologic response from the platelet-derived growth factor B (PDGF B) gene: procollagen synthesis induced by TGF-β1 was greater, and cellular proliferation was less prominent. These findings show that TGF-β1 differentially modulates extracellular matrix production and cellular proliferation in the arterial wall in vivo and could play a reparative role in the response to arterial injury.",
keywords = "cellular proliferation, extracellular matrix, gene expression, gene transfer",
author = "Nabel, {E. G.} and L. Shum and Pompili, {V. J.} and Yang, {Z. Y.} and H. San and {Hong Bing Shu}, {Bing Shu} and S. Liptay and L. Gold and D. Gordon and R. Derynck and Nabel, {G. J.}",
year = "1993",
month = "11",
day = "30",
doi = "10.1073/pnas.90.22.10759",
language = "English (US)",
volume = "90",
pages = "10759--10763",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "22",

}

TY - JOUR

T1 - Direct transfer of transforming growth factor β1 gene into arteries stimulates fibrocellular hyperplasia

AU - Nabel, E. G.

AU - Shum, L.

AU - Pompili, V. J.

AU - Yang, Z. Y.

AU - San, H.

AU - Hong Bing Shu, Bing Shu

AU - Liptay, S.

AU - Gold, L.

AU - Gordon, D.

AU - Derynck, R.

AU - Nabel, G. J.

PY - 1993/11/30

Y1 - 1993/11/30

N2 - The arterial wall responds to thrombosis or mechanical injury through the induction of specific gene products that increase cellular proliferation and connective tissue formation. These changes result in intimal hyperplasia that is observed in restenosis and the early phases of atherosclerosis. Transforming growth factor β1 (TGF-β1) is a secreted multi-functional protein that plays an important role in embryonal development and in repair following tissue injury. However, the function of TGF-β1 in vascular cell growth in vivo has not been defined. In this report, we have evaluated the role of TGF-β1 in the pathophysiology of intimal and medial hyperplasia by gene transfer of an expression plasmid encoding active TGF-β1 into porcine arteries. Expression of TGF-β1 in normal arteries resulted in substantial extracellular matrix production accompanied by intimal and medial hyperplasia. Increased procollagen, collagen, and proteoglycan synthesis in the neointima was demonstrated by immunohistochemistry relative to control transfected arteries. Expression of TGF-β1 induced a distinctly different program of gene expression and biologic response from the platelet-derived growth factor B (PDGF B) gene: procollagen synthesis induced by TGF-β1 was greater, and cellular proliferation was less prominent. These findings show that TGF-β1 differentially modulates extracellular matrix production and cellular proliferation in the arterial wall in vivo and could play a reparative role in the response to arterial injury.

AB - The arterial wall responds to thrombosis or mechanical injury through the induction of specific gene products that increase cellular proliferation and connective tissue formation. These changes result in intimal hyperplasia that is observed in restenosis and the early phases of atherosclerosis. Transforming growth factor β1 (TGF-β1) is a secreted multi-functional protein that plays an important role in embryonal development and in repair following tissue injury. However, the function of TGF-β1 in vascular cell growth in vivo has not been defined. In this report, we have evaluated the role of TGF-β1 in the pathophysiology of intimal and medial hyperplasia by gene transfer of an expression plasmid encoding active TGF-β1 into porcine arteries. Expression of TGF-β1 in normal arteries resulted in substantial extracellular matrix production accompanied by intimal and medial hyperplasia. Increased procollagen, collagen, and proteoglycan synthesis in the neointima was demonstrated by immunohistochemistry relative to control transfected arteries. Expression of TGF-β1 induced a distinctly different program of gene expression and biologic response from the platelet-derived growth factor B (PDGF B) gene: procollagen synthesis induced by TGF-β1 was greater, and cellular proliferation was less prominent. These findings show that TGF-β1 differentially modulates extracellular matrix production and cellular proliferation in the arterial wall in vivo and could play a reparative role in the response to arterial injury.

KW - cellular proliferation

KW - extracellular matrix

KW - gene expression

KW - gene transfer

UR - http://www.scopus.com/inward/record.url?scp=0027497117&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027497117&partnerID=8YFLogxK

U2 - 10.1073/pnas.90.22.10759

DO - 10.1073/pnas.90.22.10759

M3 - Article

C2 - 8248168

AN - SCOPUS:0027497117

VL - 90

SP - 10759

EP - 10763

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 22

ER -