Local overexpression of monocyte chemoattractant protein-1 at vessel wall induces infiltration of macrophages and formation of atherosclerotic lesion: Synergism with hypercholesterolemia

Masayuki Namiki, Seinosuke Kawashima, Tomoya Yamashita, Masanori Ozaki, Tetsuaki Hirase, Tatsuro Ishida, Nobutaka Inoue, Ken Ichi Hirata, Akihiro Matsukawa, Ryuichi Morishita, Yasufumi Kaneda, Mitsuhiro Yokoyama

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Monocyte/macrophage infiltration to the arterial wall is an initial step in atherosclerosis, and monocyte chemoattractant protein-1 (MCP-1) is thought to play a central role in the recruitment of these cells. In the present study, we examined the role of local expression of MCP-1 at the vessel wall in the initiation and development of atherosclerosis. We transfected the cDNA encoding rat MCP-1 into the vessel wall of the rabbit carotid artery with the use of the hemagglutinating virus of Japan (HVJ)-liposome method. The rabbits were divided into the following groups: (1) those fed normal chow and transfected with MCP-1-HVJ, (2) those fed a high cholesterol diet (1% cholesterol) and transfected with MCP-1-HVJ, and (3) those fed a high cholesterol diet and transfected with control-HVJ. Prescribed diets were started 2 weeks before transfection and were continued for another 2 weeks. In group 1, vascular lesion formation was not found, and anti-rabbit monocyte/macrophage antibody (RAM-11) staining for monocytes/macrophages was negative, although anti-rat MCP-1 antibody (R-17) staining for rat MCP-1 was positive mainly in endothelial cells. Cholesterol feeding increased plasma cholesterol levels to 1801±444 mg/dL in group 2. In group 2, all rabbits displayed neointimal formation with infiltration of RAM-11-positive cells, and a part of the lesion was also positive for Sudan III lipid staining. In group 3, hypercholesterolemia did not induce the infiltration of monocytes/macrophages and subsequent lesion formation in the vessel wall despite definite upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 on the endothelium. To initiate atherosclerotic changes, local MCP-1 overexpression at the vessel is not sufficient, and activation of other factors induced by hypercholesterolemia is required.

Original languageEnglish
Pages (from-to)115-120
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume22
Issue number1
DOIs
Publication statusPublished - 2002
Externally publishedYes

Keywords

  • Atherosclerosis
  • Hypercholesterolemia
  • Monocyte chemoattractant protein-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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