PMID- 15175640 OWN - NLM STAT- MEDLINE DCOM- 20040920 LR - 20121115 IS - 0969-7128 (Print) IS - 0969-7128 (Linking) VI - 11 IP - 16 DP - 2004 Aug TI - Antimonocyte chemoattractant protein-1 gene therapy reduces experimental in-stent restenosis in hypercholesterolemic rabbits and monkeys. PG - 1273-82 AB - 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. FAU - Ohtani, K AU - Ohtani K AD - Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. FAU - Usui, M AU - Usui M FAU - Nakano, K AU - Nakano K FAU - Kohjimoto, Y AU - Kohjimoto Y FAU - Kitajima, S AU - Kitajima S FAU - Hirouchi, Y AU - Hirouchi Y FAU - Li, X-H AU - Li XH FAU - Kitamoto, S AU - Kitamoto S FAU - Takeshita, A AU - Takeshita A FAU - Egashira, K AU - Egashira K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Gene Ther JT - Gene therapy JID - 9421525 RN - 0 (Chemokine CCL2) RN - 0 (Chemokines) RN - 0 (Chemotactic Factors) RN - 0 (Cytokines) SB - IM MH - Animals MH - Antibody Formation MH - Chemokine CCL2/*genetics MH - Chemokines/genetics MH - Chemotactic Factors/*genetics MH - Coronary Restenosis/prevention & control MH - Cytokines/genetics MH - Gene Expression/genetics MH - Genetic Therapy/*methods MH - Hyperplasia MH - Macaca fascicularis MH - Male MH - Muscle, Skeletal MH - Polymerase Chain Reaction/methods MH - Prosthesis Failure MH - Rabbits MH - Recombination, Genetic MH - *Stents MH - Transfection EDAT- 2004/06/04 05:00 MHDA- 2004/09/21 05:00 CRDT- 2004/06/04 05:00 PHST- 2004/06/04 05:00 [pubmed] PHST- 2004/09/21 05:00 [medline] PHST- 2004/06/04 05:00 [entrez] AID - 3302288 [pii] AID - 10.1038/sj.gt.3302288 [doi] PST - ppublish SO - Gene Ther. 2004 Aug;11(16):1273-82. doi: 10.1038/sj.gt.3302288.