Gene therapy for vascular smooth muscle cell proliferation after arterial injury

Takeshi Ohno, David Gordon, Hong San, Vincent J. Pompili, Michael J. Imperiale, Gary J. Nabel, Elizabeth G. Nabel

Research output: Contribution to journalArticle

390 Citations (Scopus)

Abstract

Accumulation of vascular smooth muscle cells as a consequence of arterial injury is a major feature of vascular proliferative disorders. Molecular approaches to the inhibition of smooth muscle cell proliferation in these settings could potentially limit intimal expansion. This problem was approached by introducing adenoviral vectors encoding the herpesvirus thymidine kinase (tk) into porcine arteries that had been injured by a balloon on a catheter. These smooth muscle cells were shown to be infectable with adenoviral vectors, and introduction of the tk gene rendered them sensitive to the nucleoside analog ganciclovir. When this vector was introduced into porcine arteries immediately after a balloon injury, intimal hyperplasia decreased after a course of ganciclovir treatment. No major local or systemic toxicities were observed. These data suggest that transient expression of an enzyme that catalyzes the formation of a cytotoxic drug locally may limit smooth muscle cell proliferation in response to balloon injury.

Original languageEnglish (US)
Pages (from-to)781-784
Number of pages4
JournalScience
Volume265
Issue number5173
DOIs
StatePublished - Jan 1 1994

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Vascular Smooth Muscle
Genetic Therapy
Smooth Muscle Myocytes
Cell Proliferation
Tunica Intima
Ganciclovir
Thymidine Kinase
Wounds and Injuries
Swine
Arteries
Herpesviridae
Nucleosides
Hyperplasia
Blood Vessels
Catheters
Enzymes
Pharmaceutical Preparations
Genes
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Ohno, T., Gordon, D., San, H., Pompili, V. J., Imperiale, M. J., Nabel, G. J., & Nabel, E. G. (1994). Gene therapy for vascular smooth muscle cell proliferation after arterial injury. Science, 265(5173), 781-784. https://doi.org/10.1126/science.8047883

Gene therapy for vascular smooth muscle cell proliferation after arterial injury. / Ohno, Takeshi; Gordon, David; San, Hong; Pompili, Vincent J.; Imperiale, Michael J.; Nabel, Gary J.; Nabel, Elizabeth G.

In: Science, Vol. 265, No. 5173, 01.01.1994, p. 781-784.

Research output: Contribution to journalArticle

Ohno, T, Gordon, D, San, H, Pompili, VJ, Imperiale, MJ, Nabel, GJ & Nabel, EG 1994, 'Gene therapy for vascular smooth muscle cell proliferation after arterial injury', Science, vol. 265, no. 5173, pp. 781-784. https://doi.org/10.1126/science.8047883
Ohno T, Gordon D, San H, Pompili VJ, Imperiale MJ, Nabel GJ et al. Gene therapy for vascular smooth muscle cell proliferation after arterial injury. Science. 1994 Jan 1;265(5173):781-784. https://doi.org/10.1126/science.8047883
Ohno, Takeshi ; Gordon, David ; San, Hong ; Pompili, Vincent J. ; Imperiale, Michael J. ; Nabel, Gary J. ; Nabel, Elizabeth G. / Gene therapy for vascular smooth muscle cell proliferation after arterial injury. In: Science. 1994 ; Vol. 265, No. 5173. pp. 781-784.
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