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Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene.

Publication ,  Journal Article
von der Leyen, HE; Gibbons, GH; Morishita, R; Lewis, NP; Zhang, L; Nakajima, M; Kaneda, Y; Cooke, JP; Dzau, VJ
Published in: Proc Natl Acad Sci U S A
February 14, 1995

It is postulated that vascular disease involves a disturbance in the homeostatic balance of factors regulating vascular tone and structure. Recent developments in gene transfer techniques have emerged as an exciting therapeutic option to treat vascular disease. Several studies have established the feasibility of direct in vivo gene transfer into the vasculature by using reporter genes such as beta-galactosidase or luciferase. To date no study has documented therapeutic effects with in vivo gene transfer of a cDNA encoding a functional enzyme. This study tests the hypothesis that endothelium-derived nitric oxide is an endogenous inhibitor of vascular lesion formation. After denudation by balloon injury of the endothelium of rat carotid arteries, we restored endothelial cell nitric oxide synthase (ec-NOS) expression in the vessel wall by using the highly efficient Sendai virus/liposome in vivo gene transfer technique. ec-NOS gene transfection not only restored NO production to levels seen in normal untreated vessels but also increased vascular reactivity of the injured vessels. Neointima formation at day 14 after balloon injury was inhibited by 70%. These findings provide direct evidence that NO is an endogenous inhibitor of vascular lesion formation in vivo (by inhibiting smooth muscle cell proliferation and migration) and suggest the possibility of ec-NOS transfection as a potential therapeutic approach to treat neointimal hyperplasia.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 14, 1995

Volume

92

Issue

4

Start / End Page

1137 / 1141

Location

United States

Related Subject Headings

  • Vascular Diseases
  • Tunica Intima
  • Transfection
  • Rats
  • Nitric Oxide Synthase
  • Genetic Therapy
  • Endothelium, Vascular
  • DNA, Complementary
  • Animals
  • Amino Acid Oxidoreductases
 

Citation

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von der Leyen, H. E., Gibbons, G. H., Morishita, R., Lewis, N. P., Zhang, L., Nakajima, M., … Dzau, V. J. (1995). Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene. Proc Natl Acad Sci U S A, 92(4), 1137–1141. https://doi.org/10.1073/pnas.92.4.1137
Leyen, H. E. von der, G. H. Gibbons, R. Morishita, N. P. Lewis, L. Zhang, M. Nakajima, Y. Kaneda, J. P. Cooke, and V. J. Dzau. “Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene.Proc Natl Acad Sci U S A 92, no. 4 (February 14, 1995): 1137–41. https://doi.org/10.1073/pnas.92.4.1137.
von der Leyen HE, Gibbons GH, Morishita R, Lewis NP, Zhang L, Nakajima M, et al. Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1137–41.
von der Leyen, H. E., et al. “Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene.Proc Natl Acad Sci U S A, vol. 92, no. 4, Feb. 1995, pp. 1137–41. Pubmed, doi:10.1073/pnas.92.4.1137.
von der Leyen HE, Gibbons GH, Morishita R, Lewis NP, Zhang L, Nakajima M, Kaneda Y, Cooke JP, Dzau VJ. Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1137–1141.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

February 14, 1995

Volume

92

Issue

4

Start / End Page

1137 / 1141

Location

United States

Related Subject Headings

  • Vascular Diseases
  • Tunica Intima
  • Transfection
  • Rats
  • Nitric Oxide Synthase
  • Genetic Therapy
  • Endothelium, Vascular
  • DNA, Complementary
  • Animals
  • Amino Acid Oxidoreductases