In vitro suppression of vascular smooth muscle cell proliferation using adenovirus-mediated transfer of the cd gene

摘要

Objective : To develop a treatment strategy for restenosis with a replication-deficient recombinant adenovirus (AdCMVCD) containing the cd gent whose gene product phosphorylates the prodrug 5-flurocytosine to form a nucleoside analog that inhibits DNA synthesis. Methods: Cultured primary rabbit smooth muscle cell (SMC) infected with AdCMVCD was incubated in 5- flurocytosine-containing medium and assayed with a Coulter Counter on day 2, 6, 10, and 14 for the establish- ment of proliferation curves. In addition, to observe an inhibitory effect on neighboring SMC, only a portion of the SMC population received the cd transgene. Results : The antiproliferative effect of AdCMVCD was dependent on both concentation of virus and concentration of 5-flurocytosine . Transformed cells demonstrated a bystander effect wherein SMC expressing cd gene exerted an antiproliferative effect on neighboring cells that did not express cd gene . Conclusion:Theresult demonstrates the potential utility of adenovirus-mediated cd gene transfer for the treatment of restenosis after balloon injury.