GENE-THERAPY FOR VASCULAR SMOOTH-MUSCLE CELL-PROLIFERATION AFTER ARTERIAL INJURY

Accumulation of vascular smooth muscle cells as a consequence of arter ial injury is a major feature of vascular proliferative disorders. Mol ecular approaches to the inhibition of smooth muscle cell proliferatio n in these settings could potentially limit intimal expansion. This pr oblem was approached by introducing adenoviral vectors encoding the he rpesvirus thymidine kinase (tk) into porcine arteries that had been in jured 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. Whe n this vector was introduced into porcine arteries immediately after a balloon injury, intimal hyperplasia decreased after a course of ganci clovir treatment. No major local or systemic toxicities were observed. These data suggest that transient expression of an enzyme that cataly zes the formation of a cytotoxic drug locally may limit smooth muscle cell proliferation in response to balloon injury.