Abstract: To investigate the feasibility of transduction with the herpes simplex virus thymidine kinase(HSV-tk) gene combined with ganciclovir(GCV) treatment, a recently proposed gene therapy strategy for restenosis after balloon angioplasty of the coronary arteries, a replicationdefective retrovirus containing the HSV-tk gene was constructed, and the inhibitory effect of the strategy on both vascular smooth muscle cell(VSMC) proliferation and neointima formation was observed in vitro and in a rat aorta model of restenosis, respectively. The result showed that the strategy inhibited cultured VSMCs proliferation, which was dosedependent on GCV. The bystander effect, which was previously demonstrated in malignancies, proved existent in cultured VSMC as well. In the rat aorta model of restenosis, the strategy was shown to reduce injuryinduced neointimal expansion. In contrast,neither transduction with the HSV-tk gene nor GCV treatment independently produced the antiproliferative effect both in vitro and in vi sis; gene therapy The Second Affiliated Hospital, Hebei Medical Universityvo. The data suggests the potential utility of this gene therapy strategy for human restenosis after the balloon angioplasty.

Key words: herpes simplex virus thymidine kinase gene, vascular smooth muscle cell, resteno, gene therapy