[Stent-based local delivery of therapeutic adenovirus effectively reduces neointimal proliferation in porcine coronaries].

OBJECTIVE

To find an effective means for delivering therapeutic genes of Tissue inhibitor of metalloproteinase-3 (TIMP-3) to the target sites of the dilated coronary artery for the purpose of preventing restenosis of the injured artery.

METHODS

A stainless steel stent coated with a high-molecular-mass polymer phosphorylocholine, after treatment with recombinant replication-defective adenovirus designated as RAD TIMP-3, was implanted into the coronary arteries of 7 pigs (therapy group). Another 7 pigs serving as the control group received implantation of uncoated stent. In both groups, coronary artery angiography was performed before withdrawal of intubation and 28 days after the implantation. For the purpose of planimetric analysis, the stented coronary arteries were isolated and fixed followed by resin embedding. Six sections were obtained for each stent for morphological assessment.

RESULTS

The lumen diameter of the therapy group was 2.32+/-0.18 mm, significantly greater than that of the control group (1.79+/-0.31 mm, P=0.014). The neointimal thickness was smaller in the therapy group (0.34+/-0.17 mm vs 0.81+/-0.32 mm, P=0.0 059).

CONCLUSIONS

The stent with biosynthetic coating effectively promotes TIMP3 AdV transduction and transcription, which effectively reduces neointimal proliferation, thus confirming its role in the prevention of in-stent restenosis. This maneuver may offer an alternative to conventional drug coatings for preventing restenosis.