Antimonocyte chemoattractant protein-1 gene therapy reduces experimental in-stent restenosis in hypercholesterolemic rabbits and monkeys.
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.
Ohtani
K
K
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Usui
M
M
Nakano
K
K
Kohjimoto
Y
Y
Kitajima
S
S
Hirouchi
Y
Y
Li
X-H
XH
Kitamoto
S
S
Takeshita
A
A
Egashira
K
K
D000818:Animals; D000917:Antibody Formation; D018932:Chemokine CCL2 / Q000235:genetics*; D018925:Chemokines / Q000235:genetics; D002630:Chemotactic Factors / Q000235:genetics*; D023903:Coronary Restenosis / Q000517:prevention & control; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006965:Hyperplasia; D008252:Macaca fascicularis; D008297:Male; D018482:Muscle, Skeletal; D016133:Polymerase Chain Reaction / Q000379:methods; D011475:Prosthesis Failure; D011817:Rabbits; D011995:Recombination, Genetic; D015607:Stents; D014162:Transfection
D018932:Chemokine CCL2; D018925:Chemokines; D002630:Chemotactic Factors; D016207:Cytokines