In vivo suppression of injury-induced vascular smooth muscle cell accumulation using adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene.

• DOI: 10.1073/pnas.91.22.10732
• Publication Date: 2006-05-31T12:58:56Z
• Authors: R J Guzman; E A Hirschowitz; S L Brody; R G Crystal; S E Epstein; T Finkel
• Keywords: Thymidine kinase; Nucleoside analogue

Restenosis, a process characterized in part by excessive smooth muscle cell (SMC) proliferation areas of vascular injury, occurs up to 50% patients undergoing balloon angioplasty. In an effort develop treatment strategy for restenosis, we constructed replication-deficient recombinant adenovirus (AdMLP.HSTK) containing the herpes simplex virus thymidine kinase gene (HSV tk). This viral product phosphorylates prodrug ganciclovir form nucleoside analog that inhibits DNA synthesis. Cultured primary rat SMCs infected with AdMLP.HSTK were completely growth-inhibited incubation ganciclovir-containing medium. addition, when only portion SMC population received HSV tk transgene, inhibitory effect on neighboring was evident. Evaluation this vivo using carotid injury model demonstrated local infection injured arteries AdMLP.-HSTK followed 2 weeks systemic significantly (P < 0.01) reduced injury-induced accumulation. contrast, there no suppression accumulation animals but not receiving or those control and either treated ganciclovir. These results demonstrate potential utility adenovirus-mediated transfer restenosis after injury.