PMID- 17885211 OWN - NLM STAT- MEDLINE DCOM- 20071211 LR - 20121115 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 27 IP - 12 DP - 2007 Dec TI - Local delivery of anti-monocyte chemoattractant protein-1 by gene-eluting stents attenuates in-stent stenosis in rabbits and monkeys. PG - 2563-8 AB - 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. FAU - Egashira, Kensuke AU - Egashira K AD - Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. egashira@cardiol.med.kyushu-u.ac.jp FAU - Nakano, Kaku AU - Nakano K FAU - Ohtani, Kisho AU - Ohtani K FAU - Funakoshi, Kouta AU - Funakoshi K FAU - Zhao, Gang AU - Zhao G FAU - Ihara, Yoshiko AU - Ihara Y FAU - Koga, Jun-Ichiro AU - Koga J FAU - Kimura, Satoshi AU - Kimura S FAU - Tominaga, Ryuji AU - Tominaga R FAU - Sunagawa, Kenji AU - Sunagawa K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070920 PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (Biocompatible Materials) RN - 0 (Chemokine CCL2) RN - 0 (Metals) SB - IM MH - Animals MH - Arterial Occlusive Diseases/etiology/genetics/metabolism/pathology/*prevention & control MH - Biocompatible Materials MH - Cells, Cultured MH - Chemokine CCL2/genetics/*metabolism MH - Chemotaxis, Leukocyte MH - Constriction, Pathologic/prevention & control MH - Disease Models, Animal MH - Feasibility Studies MH - *Gene Transfer Techniques MH - Genetic Therapy/*methods MH - Humans MH - Iliac Artery/pathology/*surgery MH - Kinetics MH - Leukocytes, Mononuclear/pathology MH - Macaca fascicularis MH - Macrophages/pathology MH - Male MH - Metals MH - Mutation MH - Plasmids/metabolism MH - Prosthesis Design MH - Rabbits MH - *Stents MH - Time Factors MH - Tunica Intima/pathology MH - Vascular Surgical Procedures/adverse effects/*instrumentation EDAT- 2007/09/22 09:00 MHDA- 2007/12/12 09:00 CRDT- 2007/09/22 09:00 PHST- 2007/09/22 09:00 [pubmed] PHST- 2007/12/12 09:00 [medline] PHST- 2007/09/22 09:00 [entrez] AID - ATVBAHA.107.154609 [pii] AID - 10.1161/ATVBAHA.107.154609 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2563-8. doi: 10.1161/ATVBAHA.107.154609. Epub 2007 Sep 20.