Antimonocyte chemoattractant protein-1 gene therapy reduces experimental in-stent restenosis in hypercholesterolemic rabbits and monkeys

K. Ohtani, M. Usui, K. Nakano, Y. Kohjimoto, S. Kitajima, Y. Hirouchi, X. H. Li, S. Kitamoto, A. Takeshita, K. Egashira

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1273-1282
Number of pages10
JournalGene Therapy
Volume11
Issue number16
DOIs
Publication statusPublished - Aug 1 2004

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Chemokine CCL2
Chemotactic Factors
Genetic Therapy
Stents
Haplorhini
Rabbits
Proteins
Hyperplasia
Inflammation
Mutant Proteins
Foreign Bodies
Genes
Prostheses and Implants
Transfection
Monocytes
Skeletal Muscle
Cytokines
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Antimonocyte chemoattractant protein-1 gene therapy reduces experimental in-stent restenosis in hypercholesterolemic rabbits and monkeys. / Ohtani, K.; Usui, M.; Nakano, K.; Kohjimoto, Y.; Kitajima, S.; Hirouchi, Y.; Li, X. H.; Kitamoto, S.; Takeshita, A.; Egashira, K.

In: Gene Therapy, Vol. 11, No. 16, 01.08.2004, p. 1273-1282.

Research output: Contribution to journalArticle

Ohtani, K, Usui, M, Nakano, K, Kohjimoto, Y, Kitajima, S, Hirouchi, Y, Li, XH, Kitamoto, S, Takeshita, A & Egashira, K 2004, 'Antimonocyte chemoattractant protein-1 gene therapy reduces experimental in-stent restenosis in hypercholesterolemic rabbits and monkeys', Gene Therapy, vol. 11, no. 16, pp. 1273-1282. https://doi.org/10.1038/sj.gt.3302288
Ohtani, K. ; Usui, M. ; Nakano, K. ; Kohjimoto, Y. ; Kitajima, S. ; Hirouchi, Y. ; Li, X. H. ; Kitamoto, S. ; Takeshita, A. ; Egashira, K. / Antimonocyte chemoattractant protein-1 gene therapy reduces experimental in-stent restenosis in hypercholesterolemic rabbits and monkeys. In: Gene Therapy. 2004 ; Vol. 11, No. 16. pp. 1273-1282.
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