Monocyte Chemoattractant Protein-1 is an Essential Inflammatory Mediator in Angiotensin II-Induced Progression of Established Atherosclerosis in Hypercholesterolemic Mice

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

Research output: Contribution to journalArticlepeer-review

91 Citations (Scopus)

Abstract

Objective-Chronic inflammatory processes might be involved in the progression and destabilization of atherosclerotic plaques. Therefore, identification of the mechanism underlying arterial inflammatory function might lead to the development of novel therapeutic strategies. Angiotensin II (AngII) is implicated in atherogenesis by activating the vascular inflammation system, mainly through monocyte chemotaxis. Therefore, we hypothesized that AngII increases plaque size and promotes destabilization of established atheromas by activating the monocyte chemoattractant protein-1 (MCP-1) pathway. Methods and Results-We report here that 4-week infusion of AngII not only increased plaque size but also induced a destabilization phenotype (ie, increased macrophages and lipids and decreased collagen and smooth muscle cells) of pre-existing atherosclerotic lesions of hypercholesterolemic mice. AngII also enhanced the gene expression of inflammatory cytokines (TNFα, IL-6, etc.) and chemokines (MCP-1, CCR2, etc). Blockade of MCP-1, by transfecting the deletion mutant of the human MCP-1 gene into the skeletal muscles, limited AngII-induced progression and destabilization of established atherosclerotic lesions and suppressed the induction of proinflammatory genes. Conclusions-These data suggest that MCP-1 functions as a central inflammatory mediator in the AngII-induced progression and changes in plaque composition of established atheroma.

Original languageEnglish
Pages (from-to)534-539
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume24
Issue number3
DOIs
Publication statusPublished - Mar 2004

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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