Essential role of monocyte chemoattractant protein-1 in development of restenotic changes (neointimal hyperplasia and constrictive remodeling) after balloon angioplasty in hypercholesterolemic rabbits.
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.
Mori
Emiko
E
Department of Surgery and Science, Kyushu University School of Medical Sciences, Fukuoka, Japan.
Komori
Kimihiro
K
Yamaoka
Terutoshi
T
Tanii
Mitsugu
M
Kataoka
Chu
C
Takeshita
Akira
A
Usui
Makoto
M
Egashira
Kensuke
K
Sugimachi
Keizo
K
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
D018932:Chemokine CCL2; D012333:RNA, Messenger