Local delivery of anti-monocyte chemoattractant protein-1 by gene-eluting Stents attenuates in-stent stenosis in rabbits and monkeys
Local delivery of anti-monocyte chemoattractant protein-1 by gene-eluting Stents attenuates in-stent stenosis in rabbits and monkeys
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DOI：
10.1161/atvbaha.107.154609
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发表时间：
2007-12-01
影响因子：
8.7
通讯作者：
Sunagawa, Kenji
中科院分区：
文献类型：
--
作者：
Egashira, Kensuke;Nakano, Kaku;Sunagawa, Kenji
目的：我们先前已经证明，肌肉内转移抗单核细胞趋化蛋白-1(MCP-1)基因(称为7ND)能够预防实验性再狭窄。本研究的目的是通过基因洗脱支架局部转导7ND基因来减少支架内新生内膜形成的有效性和安全性。方法和结果：我们在体外发现，7ND有效地抑制了单核白细胞的趋化作用，也抑制了血管平滑肌细胞的增殖和迁移。然后，我们用一种含有携带7ND基因的质粒的生物相容性聚合物包覆支架，并将这些支架部署在兔和猴子的髂动脉。7ND基因洗脱支架在1个月后可减少支架相关的单核细胞的浸润和新生内膜的形成，并在1、3和6个月时对猴的新生内膜形成有长期的抑制作用。结论：用7ND基因洗脱支架抑制MCP-1的作用可减少支架内新生内膜的形成，且无不良反应。7ND基因洗脱支架可能是治疗人类再狭窄的一种有前途的治疗方法。
Objective-We have previously shown that the intramuscular transfer of the anti-monocyte chemoattractant protein-1 (MCP-1) gene (called 7ND) is able to prevent experimental restenosis. The aim of this study was to determine the in vivo efficacy and safety of local delivery of 7ND gene via the gene-eluting stent in reducing in-stent neointima formation in rabbits and in cynomolgus monkeys.Methods and Results-We here found that in vitro, 7ND effectively inhibited the chemotaxis of mononuclear leukocytes and also inhibited the proliferation/ migration of vascular smooth muscle cells. We then coated stents with a biocompatible polymer containing a plasmid bearing the 7ND gene, and deployed these stents in the iliac arteries of rabbits and monkeys. 7ND gene- eluting stents attenuated stent-associated monocyte infiltration and neointima formation after one month in rabbits, and showed long-term inhibitory effects on neointima formation when assessments were carried out at 1, 3, and 6 months in monkeys.Conclusions-Strategy of inhibiting the action of MCP-1 with a 7ND gene- eluting stent reduced in-stent neointima formation with no evidence of adverse effects in rabbits and monkeys. The 7ND gene-eluting stent could be a promising therapy for treatment of restenosis in humans.