Anti-monocyte chemoattractant protein-1 gene therapy limits progression and destabilization of established atherosclerosis in apolipoprotein E-knockout mice

Shujiro Inoue, Kensuke Egashira, Weihua Ni, Shiro Kitamoto, Makoto Usui, Kisho Otani, Minako Ishibashi, Ken Ichi Hiasa, Ken Ichi Nishida, Akira Takeshita

Research output: Contribution to journalArticlepeer-review

222 Citations (Scopus)

Abstract

Background - Monocyte infiltration into the arterial wall and its activation is the central event in atherogenesis. Thus, monocyte chemoattractant protein-1 (MCP-1) might be a novel therapeutic target against atherogenesis. We and others recently reported that blockade or abrogation of the MCP-1 pathway attenuates the initiation of atheroma formation in hypercholesterolemic mice. It remains unclear, however, whether blockade of MCP-1 can limit progression or destabilization of established lesions. Methods and Results - We report here that blockade of MCP-1 by transfecting an N-terminal deletion mutant of the MCP-1 gene limited progression of preexisting atherosclerotic lesions in the aortic root in hypercholesterolemic mice. In addition, blockade of MCP-1 changed the lesion composition into a more stable phenotype, ie, containing fewer macrophages and lymphocytes, less lipid, and more smooth muscle cells and collagen. This strategy decreased expression of CD40 and the CD40 ligand in the atherosclerotic plaque and normalized the increased chemokine (RANTES and MCP-1) and cytokine (tumor necrosis factor α, interleukin-6, interleukin-1β, and transforming growth factor β1) gene expression. These data suggest that MCP-1 is a central mediator in the progression and destabilization of established atheroma. Conclusions - The results of the present study suggest that the inflammatory responses mediated by MCP-1 are important in atherosclerosis and its complications.

Original languageEnglish
Pages (from-to)2700-2706
Number of pages7
JournalCirculation
Volume106
Issue number21
DOIs
Publication statusPublished - Nov 19 2002

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Anti-monocyte chemoattractant protein-1 gene therapy limits progression and destabilization of established atherosclerosis in apolipoprotein E-knockout mice'. Together they form a unique fingerprint.

Cite this