New anti-monocyte chemoattractant protein-1 gene therapy attenuates atherosclerosis in apolipoprotein E-knockout mice

W. Ni, K. Egashira, S. Kitamoto, C. Kataoka, M. Koyanagi, S. Inoue, K. Imaizumi, C. Akiyama, K. I. Nishida, A. Takeshita

Research output: Contribution to journalArticlepeer-review

213 Citations (Scopus)

Abstract

Background - Monocyte recruitment into the arterial wall and its activation may be the central event in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine for monocyte recruitment, and its receptor (CCR2) may mediate such in vivo response. Although the importance of the MCP-1/CCR2 pathway in atherogenesis has been clarified, it remains unanswered whether postnatal blockade of the MCP-1 signals could be a unique site-specific gene therapy. Methods and Results - We devised a new strategy for anti-MCP-1 gene therapy to treat atherosclerosis by transfecting an N-terminal deletion mutant of the human MCP-1 gene into a remote organ (skeletal muscle) in apolipoprotein E-knockout mice. This strategy effectively blocked MCP-1 activity and inhibited the formation of atherosclerotic lesions but had no effect on serum lipid concentrations. Furthermore, this strategy increased the lesional extracellular matrix content. Conclusions - We conclude that this anti-MCP-1 gene therapy may serve not only to reduce atherogenesis but also to stabilize vulnerable atheromatous plaques. This strategy may be a useful and feasible form of gene therapy against atherosclerosis in humans.

Original languageEnglish
Pages (from-to)2096-2101
Number of pages6
JournalCirculation
Volume103
Issue number16
DOIs
Publication statusPublished - Apr 24 2001

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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