Research Article
Gene Therapy (2004) 11, 1273–1282. doi:10.1038/sj.gt.3302288 Published online 3 June 2004
Antimonocyte chemoattractant protein-1 gene therapy reduces experimental in-stent restenosis in hypercholesterolemic rabbits and monkeys
K Ohtani1, M Usui1, K Nakano1, Y Kohjimoto2, S Kitajima2, Y Hirouchi2, X-H Li3, S Kitamoto1, A Takeshita1 and K Egashira1
- 1Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- 2Primate Research Center, Guandong, China
- 3Gaoyao Kangda Laboratory Animals Science and Technology, Guandong, China
Correspondence: Dr K Egashira, Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Received 12 October 2003; Accepted 19 March 2004; Published online 3 June 2004.
Abstract
In-stent restenosis results exclusively from neointimal hyperplasia due to mechanical injury and a foreign body response to the prosthesis. Inflammation mediated by monocyte chemoattractant protein-1 (MCP-1) might therefore underlie in-stent restenosis. We recently devised a new strategy for anti-MCP-1 gene therapy by transfecting an N-terminal deletion mutant of the MCP-1 gene into skeletal muscles. We used this strategy to investigate the role of MCP-1 in experimental in-stent restenosis in hypercholesterolemic rabbits and monkeys. Transfection of the mutant MCP-1 gene suppressed monocyte infiltration/activation in the stented arterial wall and markedly reduced the development of neointimal hyperplasia. This strategy also suppressed local expression of MCP-1 and inflammatory cytokines. Therefore, inhibition of MCP-1-mediated inflammation is effective in reducing experimental in-stent restenosis. This strategy might be a useful form of gene therapy against human in-stent restenosis.
Keywords:
monocyte, inflammation, restenosis, stent
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