Gene therapy targeting monocyte chemoattractant protein-1 for vascular disease.

Shiro Kitamoto, Kensuke Egashira

    Research output: Contribution to journalReview articlepeer-review

    21 Citations (Scopus)

    Abstract

    Monocyte chemoattractant protein-1 (MCP-1) has been shown to play an essential role in the pathogenesis of arteriosclerosis and other vascular diseases, such as restenosis after arterial injury, by recruiting monocytes into the arterial wall. We devised a new strategy for anti-MCP-1 gene therapy against arteriosclerosis by transfecting an amino-terminal deletion mutant (7ND), which lacks the amino-terminal amino acids 2 to 8 of the human MCP-1 gene, into a remote organ (skeletal muscles). Intramuscular transduction with the mutant MCP-1 gene suppressed inflammatory and proliferative changes and arteriosclerosis formation induced by the chronic inhibition of nitric oxide synthesis in rats. 7ND gene transfection also inhibited the initiation, progression, and destabilization of atherosclerosis in Apolipoprotein E-knockout mice. Moreover, the strategy reduced restenosis after balloon injury in rabbits, rats, and monkeys, or neointimal formation after stent implantation in monkeys. This new strategy may be a useful and feasible gene therapy against atherosclerosis and restenosis after angioplasty.

    Original languageEnglish
    Pages (from-to)261-265
    Number of pages5
    JournalJournal of atherosclerosis and thrombosis
    Volume9
    Issue number6
    DOIs
    Publication statusPublished - 2002

    All Science Journal Classification (ASJC) codes

    • Internal Medicine
    • Cardiology and Cardiovascular Medicine
    • Biochemistry, medical

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