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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Vydáno v:	Science (American Association for the Advancement of Science) Ročník 265; číslo 5173; s. 781 - 784
Hlavní autoři:	Ohno, Takeshi, Gordon, David, San, Hong, Pompili, Vincent J., Imperiale, Michael J., Nabel, Gary J., Nabel, Elizabeth G.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States American Society for the Advancement of Science 05.08.1994 American Association for the Advancement of Science
Témata:	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
On-line přístup:	Získat plný text
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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0036-8075 1095-9203
DOI:	10.1126/science.8047883