抄録
Recent evidence suggests that stent-associated inflammation is a prominent feature in animals and humans, and thus can be a promising next-generation target for prevention of restenosis. We have shown great benefit of anti-monocyte chemoattractant protein-1 (MCP-1) therapy by systemic transfer of an N-terminus deletion mutants of human MCP-1 (called 7ND) gene for prevention of restenotic changes in animals. Therefore, to translate our achievement on MCP-1 pathobiology to clinic, we tested the hypothesis that stent-based local delivery of 7ND gene reduces in-stent neointimal formation. Bare, polymer-coated, and 7ND plasmid-coated stents were implanted in iliac arteries of hypercholesterolemic rabbits (n=8-10 each) and cynomolgus monkeys (n=7-10 each). 7ND gene-eluting stents attenuated stent-associated monocyte infiltration/activation and neointimal formation (about 30% reduction) in rabbits. In monkeys, significant reduction of neointimal formation was noted 1, 3, and 6 month after stenting, indicating long-term benefits of 7ND gene ES in monkeys. No evidence of incomplete healing process was noted in 7ND-eluting stent sites. In conclusion, anti-MCP-1 strategy with 7ND gene-eluting stents was strikingly effective in reducing experimental restenosis in rabbits and monkeys. Our finding in nonhuman primates has significant clinical significance, implying that this anti-inflammation strategy targeting MCP-1 might be a promising therapy against human restenosis. [J Physiol Sci. 2006;56 Suppl:S42]