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

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.

journal_name

Gene Ther

journal_title

Gene therapy

authors

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

doi

10.1038/sj.gt.3302288

keywords:

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

1273-82

issue

16

eissn

0969-7128

issn

1476-5462

pii

3302288

journal_volume

11

pub_type

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