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 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.
Ohno
T
T
Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor 48109.
Gordon
D
D
San
H
H
Pompili
V J
VJ
Imperiale
M J
MJ
Nabel
G J
GJ
Nabel
E G
EG
D000256:Adenoviridae / Q000235:genetics; D000800:Angioplasty, Balloon; D000818:Animals; D001158:Arteries / Q000293:injuries*; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D015774:Ganciclovir / Q000378:metabolism / Q000627:therapeutic use; D015316:Genetic Therapy; D005822:Genetic Vectors; D006564:Herpesviridae / Q000201:enzymology; D006965:Hyperplasia; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D012008:Recurrence; D013552:Swine; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism
D013937:Thymidine Kinase; D015774:Ganciclovir