We are attempting to use the techniques of gene therapy to understand and treat vascular diseases. In particular, we are using adenovirus vectors as a way of efficiently transferring foreign genes into the vessel wall, the myocardium or an ischemic area. The two clinical problems we have attempted to study and treat with these methods all restenoses following balloon angioplasty and induction of therapeutic angiogenesis in areas of arterial insufficiency. Over the last year we have screened several candidate genes which inhibit smooth muscle cell (smc) proliferation or induce smc programmed cell death in animal models of restenosis. We have also begun studies to test whether adenoviral delivery of vascular endothelial cell growth factor (VEGF) induces collateral blood vessel growth in vivo.