Gene Therapy for Vascular Smooth Muscle Cell Proliferation After Arterial Injury

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...

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Published in:Science (American Association for the Advancement of Science) Vol. 265; no. 5173; pp. 781 - 784
Main Authors: Ohno, Takeshi, Gordon, David, San, Hong, Pompili, Vincent J., Imperiale, Michael J., Nabel, Gary J., Nabel, Elizabeth G.
Format: Journal Article
Language:English
Published: United States American Society for the Advancement of Science 05.08.1994
American Association for the Advancement of Science
Subjects:
Adenoviridae - genetics
adenovirus
Angioplasty, Balloon
Animals
Arteries
Arteries - injuries
Arteriosclerosis - etiology
Arteriosclerosis - pathology
Arteriosclerosis - therapy
Balloons
Catheters
Cell Division
Cell Survival - drug effects
Cells
Ganciclovir - metabolism
Ganciclovir - therapeutic use
Gene therapy
Genetic Therapy
Genetic Vectors
Herpesviridae - enzymology
herpesvirus
Hyperplasia
Infections
Injuries
Muscle, Smooth, Vascular - cytology
Phosphatases
Physical trauma
Recurrence
Smooth muscle myocytes
Surgery
Swine
Thymidine Kinase - genetics
Thymidine Kinase - metabolism
Vascular smooth muscle
ISSN:0036-8075, 1095-9203
Online Access:Get full text
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Summary: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.
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ISSN:0036-8075
1095-9203
DOI:10.1126/science.8047883