BackgroundSmooth muscle cell proliferation and extracellular matrix accumulation are the principal mechanisms leading to vascular restenosis. We have previously demonstrated the growth-inhibitory effect of antisense oligomers targeting the c-mycproto-oncogene in human smooth muscle cells. The goal of this study was to investigate whether c-mycantisense oligomers reduce neointimal formation in balloon-denuded porcine coronary arteries.Methods and ResultsFirst, type I collagen synthesis, which reflects synthetic function, was markedly reduced following c-mycantisense oligomers in porcine vascular smooth muscle cells independent of the growth inhibition. These effects in vitro provided the rationale for assessing c-mycantisense oligomers in the prevention of neointima in vivo. Second, the efficiency of single transcatheter delivery of oligomers into denuded porcine coronary arteries was determined. Despite rapid plasma clearance following local delivery, oligomers persisted at the site of injection for at least 3 days, exceeding by severalfold their concentration in peripheral organs. Third, morphometric analyses were carried out in balloon-denuded coronary arteries at 1 month after transcatheter c-mycan-V tisense oligomer administration. Maximal neointimal area was reduced from 0.80±0.17 mm2in the control group (n=12) to 0.24±0.06 mm2in the antisense-treated group (n= 13,P<.01). Likewise, a significant reduction in maximal neointimal thickness was observed in the antisense-treated group (P<.01). These changes in vascular remodeling following denuding injury resulted in an increase in residual lumen from 64±6% in the control group to 81±5% in the antisense-treated group (P<.05).Conclusions(1) Single transcatheter administration al-lowed for endoluminal delivery of oligomers to the site of coronary arterial injury. (2) C-mycantisense oligomers reduced the formation of neointima in denuded coronary arteries, implying a therapeutic potential of this approach for the prevention of coronary restenosis. (3) It is postulated that the c-mycproto-oncogene is involved in the process of vascular remodeling, regulating smooth muscle cell proliferation and extracellular matrix synthesis.