title: Anti-monocyte chemoattractant protein-1 gene therapy inhibits restenotic changes (neointimal hyperplasia) after balloon injury in rats and monkeys.
abstract: Prevention of restenosis after coronary intervention is a major clinical challenge, which highlights the need of new therapeutic options. Vascular injury may involve inflammatory responses that accelerate the recruitment and activation of monocytes through the activation of chemotactic factors, including monocyte chemoattractant protein-1 (MCP-1). However, there is no definitive evidence supporting the role of MCP-1 in 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 demonstrate here that this strategy suppressed monocyte infiltration/activation in the injured site and markedly inhibited restenotic changes (neointimal hyperplasia) after balloon injury of the carotid artery in rats and monkeys. This strategy also suppressed the local production of MCP-1 and inflammatory cytokines. Therefore, monocyte infiltration and activation mediated by MCP-1 are essential in the development of restenotic changes after balloon injury. This strategy may be a useful form of gene therapy against human restenosis.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Usui
authors.forename: Kensuke
authors.initials: K
authors.lastname: Egashira
authors.forename: Kisho
authors.initials: K
authors.lastname: Ohtani
authors.forename: Chu
authors.initials: C
authors.lastname: Kataoka
authors.forename: Minako
authors.initials: M
authors.lastname: Ishibashi
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hiasa
authors.forename: Makoto
authors.initials: M
authors.lastname: Katoh
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Zhao
authors.forename: Shiro
authors.initials: S
authors.lastname: Kitamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000209:etiology / Q000517:prevention & control*; D002404:Catheterization / Q000009:adverse effects; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006965:Hyperplasia; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D008297:Male; D009130:Muscle, Smooth / Q000737:chemistry; D009154:Mutation; D010957:Plasmids / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D000199:Actins; C515334:CCR2 protein, human; C515336:Ccr2 protein, rat; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D014841:von Willebrand Factor