title: Essential role of monocyte chemoattractant protein-1 in development of restenotic changes (neointimal hyperplasia and constrictive remodeling) after balloon angioplasty in hypercholesterolemic rabbits.
abstract: BACKGROUND
  Renarrowing of dilated arterial sites (restenosis) hampers the clinical benefits of coronary angioplasty. Infiltration and activation of monocytes in the arterial wall mediated by monocyte chemoattractant protein-1 (MCP-1) might be a major cause of restenosis after angioplasty. However, there is no direct evidence to support a definite role of MCP-1 in the development of restenosis. Methods and Results- 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 the development of restenotic changes after balloon injury in the carotid artery in hypercholesterolemic rabbits. Intramuscular transfection of the mutant MCP-1 gene suppressed monocyte infiltration/activation in the injured arterial wall and thus attenuated the development of neointimal hyperplasia and negative remodeling.
  
  
  CONCLUSIONS
  MCP-1-mediated monocyte infiltration is necessary in the development of restenotic changes to balloon injury in hypercholesterolemic rabbits. This strategy may be a useful and practical form of gene therapy against human restenosis.
authors.affiliation: Department of Surgery and Science, Kyushu University School of Medical Sciences, Fukuoka, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Mori
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Komori
authors.forename: Terutoshi
authors.initials: T
authors.lastname: Yamaoka
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Tanii
authors.forename: Chu
authors.initials: C
authors.lastname: Kataoka
authors.forename: Akira
authors.initials: A
authors.lastname: Takeshita
authors.forename: Makoto
authors.initials: M
authors.lastname: Usui
authors.forename: Kensuke
authors.initials: K
authors.lastname: Egashira
authors.forename: Keizo
authors.initials: K
authors.lastname: Sugimachi
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D016893:Carotid Stenosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000235:genetics / Q000502:physiology*; D003251:Constriction, Pathologic; D018274:Electroporation; D006083:Graft Occlusion, Vascular / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D006937:Hypercholesterolemia / Q000150:complications; D006965:Hyperplasia; D007700:Kinetics; D008297:Male; D009000:Monocytes / Q000502:physiology; D018482:Muscle, Skeletal; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D014463:Ultrasonography
chemical_list: D018932:Chemokine CCL2; D012333:RNA, Messenger