Essential role of monocyte chemoattractant protein-1 in development of restenotic changes (neointimal hyperplasia and constrictive remodeling) after balloon angioplasty in hypercholesterolemic rabbits

Emiko Mori, Kimihiro Komori, Terutoshi Yamaoka, Mitsugu Tanii, Chu Kataoka, Akira Takeshita, Makoto Usui, Kensuke Egashira, Keizo Sugimachi

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    124 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)2905-2910
    Number of pages6
    JournalCirculation
    Volume105
    Issue number24
    DOIs
    Publication statusPublished - Jun 18 2002

    All Science Journal Classification (ASJC) codes

    • Cardiology and Cardiovascular Medicine
    • Physiology (medical)

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